LiversPub Date : 2023-09-22DOI: 10.3390/livers3040037
Hussein Mukasa Kafeero, Dorothy Ndagire, Ponsiano Ocama, Charles Drago Kato, David Patrick Kateete, Abdul Walusansa, Ali Kudamba, Kigozi Edgar, Fred Ashaba Katabazi, Maria Magdalene Namaganda, Jamilu E. Ssenku, Eddie Wampande, Henry Kajumbula, Hakim Sendagire
{"title":"The 863C>A and 1031T>C Single Nucleotide Polymorphisms (SNPs) in the Tumor Necrosis Factor Alpha (TNF-α) Promoter Gene May Not Be Putative Predictors of HBV Endemicity","authors":"Hussein Mukasa Kafeero, Dorothy Ndagire, Ponsiano Ocama, Charles Drago Kato, David Patrick Kateete, Abdul Walusansa, Ali Kudamba, Kigozi Edgar, Fred Ashaba Katabazi, Maria Magdalene Namaganda, Jamilu E. Ssenku, Eddie Wampande, Henry Kajumbula, Hakim Sendagire","doi":"10.3390/livers3040037","DOIUrl":"https://doi.org/10.3390/livers3040037","url":null,"abstract":"Background: Genetic polymorphisms within the gene loci of the promoter region of tumor necrosis factor (TNF) alpha have been associated with the pathogenesis of hepatitis B virus (HBV) infection. In Uganda, there is a wide variation in the HBV endemicity, ranging from low endemicity, through moderate endemicity, to hyper-endemicity. However, the underlying reasons for this disparity in HBV burden are not fully elucidated. Thus, we aimed to test the hypothesis that the TNF-α-863C/A and -1031T/C polymorphic sites may have an effect on the difference between the burden of HBV in our country. We screened 384 participants, from which a sample of 134 was drawn, to determine the HBV, TNF-α-863C/A, and TNF-α-863T/C genotypes. The nucleotide BLAST was used to match the unknown targeted sequence obtained from the Sanger sequence against the known deposited sequence. This process unveiled the base substitution mutation and the HBV genotypes. The odds ratio (OR) and Chi-square test of proportions were used for the analysis. All the analyses were performed using SPSS version 26.0 and MedCalc software version 20.010 at 95% CI. A p < 0.05 was considered statistically significant. Results: The prevalence of both the TNF-α-863C/A and the TNF-α-1031T/C genotypes and their alleles did not differ significantly by endemicity (p > 0.05). However, the prevalence of the nucleotide substitution mutations for TNF-α-863C>A and TNF-α-1031T>C was significantly low for all the study groups (p < 0.05). Conclusion: The TNF-α gene promoter at the TNF-α-863C/A and 1031T/C positions is conserved in our population and may not affect the endemicity of HBV infection. However, future research should focus on the use of nationwide samples in order to reach concreate determinations regarding the role of the TNF-α polymorphisms in the risk/resolution of HBV infections in an African or Black population.","PeriodicalId":74083,"journal":{"name":"Livers","volume":"43 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136061140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
LiversPub Date : 2023-09-21DOI: 10.3390/livers3030036
Miguel Ángel Hidalgo-Blanco, Juan Carlos Lopez-Delgado, José Antonio Sarria-Guerrero
{"title":"Nutrition Therapy in Critically Ill Patients with Liver Disease: A Narrative Review","authors":"Miguel Ángel Hidalgo-Blanco, Juan Carlos Lopez-Delgado, José Antonio Sarria-Guerrero","doi":"10.3390/livers3030036","DOIUrl":"https://doi.org/10.3390/livers3030036","url":null,"abstract":"Nutrition therapy in critically ill patients with liver disease represents a challenge for Intensive Care Units (ICUs). Nutritional status is correlated with the degree of hepatic dysfunction and the presence of malnutrition worsens outcomes in these patients. The nutritional risk that critically ill patients represent, together with the pathophysiological alterations of liver disease, especially in terms of nutrition intake and protein depletion, leads to malnutrition and sarcopenia. Nutrition therapy improves the survival of these patients; however, this is challenging since they more frequently experience difficulties with nutrition delivery. In consequence, both evaluation of nutritional status and an individualized approach seem mandatory for achieving nutrition objectives. The present narrative review discusses the importance of nutrition therapy, the recommendations of contemporary clinical practice guidelines, and a practical approach to provide the best possible nutrition therapy in patients with liver disease admitted to ICUs.","PeriodicalId":74083,"journal":{"name":"Livers","volume":"22 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136236448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hepatitis E Virus: Epidemiology, Clinical Aspects, and Its Significance as a Major Pregnancy Risk","authors":"Sidra Urooj, Sadia Anjum, Fareeha Iqbal, Maisa Siddiq Abduh, Hashaam Akhtar, Sumbal Javed, Salik Javed Kakar, Aamer Ikram, Nabeel Ahmed Maqbool, Tahir Ahmad","doi":"10.3390/livers3030035","DOIUrl":"https://doi.org/10.3390/livers3030035","url":null,"abstract":"HEV is a single-stranded, positive RNA virus. The hepatitis E virus (HEV) is the causing agent of hepatitis, with a high prevalence rate in low-income countries due to poor sanitary conditions. It can exhibit acute, continuous, or extrahepatic consequences in immunocompromised individuals such as those undergoing organ transplantation and having HIV infection. HEV infection is either self limiting (silent), meaning the patient will possibly recover on his own, or symptomatic, causing acute liver injury or fulminant hepatitis and may eventually cause death. It can also cause chronic hepatitis that can progress to cirrhosis or recovery. Pregnancy-related HEV infection has an incidence rate of 30%. HEV escape from innate immunity, hormonal imbalances, defective monocyte–macrophage function, downregulation of the T-cell-mediated immune system, high cytokine production, nutritional factors, and socioeconomic conditions may play fundamental roles in the prevalence of HEV infection. It is necessary to take particular measures to reduce the incidence burden of HEV infection in high endemic locations as the incidence data, not the prevalence data, is more accurate at estimating disease dynamics. The purpose of this study is to throw light on several aspects of the hepatitis E virus and to discuss the incidence of HEV infection concerning other diseases. HEV molecular features, clinical features, epidemiology, extrahepatic manifestations, and multiple available diagnostics and treatment strategies for HEV are debated in the current review.","PeriodicalId":74083,"journal":{"name":"Livers","volume":"50 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135397332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Impact of IL-12B Genetic Variants on Antiviral Treatment Response among Hepatitis B Patients in Pakistan","authors":"Yasmin Badshah, Maria Shabbir, Sameen Zafar, Uzma Mussarat, Aamer Ikram, Sumbal Javed, Hashaam Akhtar","doi":"10.3390/livers3030034","DOIUrl":"https://doi.org/10.3390/livers3030034","url":null,"abstract":"HBV is a continuous major global health concern. Genetic factors of hosts are known to play a role in HBV infection outcomes. This study aimed to reveal the association of IL-12b 3′ UTR variant rs3212227 in HBV patients. Genotyping was performed using ARMS-PCR to detect IL-12b rs3212227 polymorphism. The patients were categorized into groups based on their response to the antiviral therapy. Group I: non-sustained virological response (NSR); Group II: sustained virological responders (SVR); and Group III: HBV-positive fresh cases. ALT levels were measured to evaluate liver function, and viral load was determined to evaluate viral infectivity among the study groups. The variant genotype CC was found to be significantly associated with the non-sustained virological response to the antiviral therapy (with a p-value of 0.0117; OR = 2.914; RR = 1.556). It was also determined that the genotype CC was the most prevalent genotype among both genders in the NSR group. Viral load was found to be 6-fold higher in Group III compared to Group I and Group II. The results suggest that genotype CC is the most prevalent genotype in the NSR groups, and it is associated with a poor response to antiviral therapy in Pakistani patients with HBV infection.","PeriodicalId":74083,"journal":{"name":"Livers","volume":"8 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135878443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
LiversPub Date : 2023-09-05DOI: 10.3390/livers3030033
Ker Ming Seaw, Christiani Jeyakumar Henry, Xinyan Bi
{"title":"Relationship between Non-Alcoholic Fatty Liver Disease and Visceral Fat Measured by Imaging-Based Body Composition Analysis: A Systematic Review","authors":"Ker Ming Seaw, Christiani Jeyakumar Henry, Xinyan Bi","doi":"10.3390/livers3030033","DOIUrl":"https://doi.org/10.3390/livers3030033","url":null,"abstract":"Imaging-based body composition analysis can quantify visceral fat, which is an important feature of lean non-alcoholic fatty liver disease (NAFLD) patients. This review assesses current evidence of the relationship between NAFLD, particularly hepatic steatosis, and visceral fat that is measured using imaging-based body composition analysis. PubMed Central and ScienceDirect were searched for studies that provided quantification of the relationship between NAFLD, hepatic steatosis and visceral fat. Twenty studies comprising 15,763 subjects were included, consisting of the relationship with NAFLD (n = 15) and the relationship with hepatic steatosis (n = 7). All studies reported a positive relationship between NAFLD and visceral fat. For hepatic steatosis regardless of severity, only one study reported no correlation with visceral fat. Further results showed that visceral fat is more related to NAFLD and hepatic steatosis in females than males. More studies including NAFLD of different stages must be performed in the future to validate the degree of association between visceral fat and NAFLD at all stages as well as this relationship difference between genders.","PeriodicalId":74083,"journal":{"name":"Livers","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44737669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
LiversPub Date : 2023-08-30DOI: 10.3390/livers3030032
Mansi Rai, Namuna Paudel, Mesevilhou Sakhrie, D. Gemmati, I. Khan, V. Tisato, Anurag Kanase, A. Schulz, Ajay Vikram Singh
{"title":"Perspective on Quantitative Structure–Toxicity Relationship (QSTR) Models to Predict Hepatic Biotransformation of Xenobiotics","authors":"Mansi Rai, Namuna Paudel, Mesevilhou Sakhrie, D. Gemmati, I. Khan, V. Tisato, Anurag Kanase, A. Schulz, Ajay Vikram Singh","doi":"10.3390/livers3030032","DOIUrl":"https://doi.org/10.3390/livers3030032","url":null,"abstract":"Biotransformation refers to the metabolic conversion of endogenous and xenobiotic chemicals into more hydrophilic substances. Xenobiotic biotransformation is accomplished by a restricted number of enzymes with broad substrate specificities. The biotransformation of xenobiotics is catalyzed by various enzyme systems that can be divided into four categories based on the reaction they catalyze. The primary concentration is in cytochrome P450, while the CYP enzymes responsible for xenobiotic biotransformation are located within the hepatic endoplasmic reticulum (microsomes). Cytochrome P450 (CYP450) enzymes are also present in extrahepatic tissues. Enzymes catalyzing biotransformation reactions often determine the intensity and duration of the action of drugs and play a key role in chemical toxicity and chemical tumorigenesis. The structure of a given biotransforming enzyme may differ among individuals, which can cause differences in the rates of xenobiotic biotransformation. The study of the molecular mechanisms underlying chemical liver injury is fundamental for preventing or devising new modalities of treatment for liver injury using chemicals. Active metabolites arise from the biotransformation of a parent drug compound using one or more xenobiotic-processing enzymes to generate metabolites with different pharmacological or toxicological properties. Understanding how exogenous chemicals (xenobiotics) are metabolized, distributed, and eliminated is critical to determining the impact of these compounds on human health. Computational tools such as Biotransformer have been developed to predict all the possible metabolites of xenobiotic and enzymatic profiles that are linked to the production of metabolites. The construction of xenobiotic metabolism maps can predict enzymes catalyzing metabolites capable of binding to DNA.","PeriodicalId":74083,"journal":{"name":"Livers","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43397317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
LiversPub Date : 2023-08-25DOI: 10.3390/livers3030031
S. Shea, C. Lionis, C. Kite, L. Atkinson, Lukasz Lagojda, Surinderjeet S. Chaggar, I. Kyrou, H. Randeva
{"title":"Challenges in the Management of Non-Alcoholic Fatty Liver Disease (NAFLD): Towards a Compassionate Approach","authors":"S. Shea, C. Lionis, C. Kite, L. Atkinson, Lukasz Lagojda, Surinderjeet S. Chaggar, I. Kyrou, H. Randeva","doi":"10.3390/livers3030031","DOIUrl":"https://doi.org/10.3390/livers3030031","url":null,"abstract":"Representing a growing ‘silent epidemic’, non-alcoholic fatty liver disease (NAFLD) affects around 25–30% of the general population. Alarmingly, NAFLD increases the risk of cardiovascular disease, both independently and through its strong associations with obesity, type 2 diabetes, and metabolic syndrome, whilst posing a substantial burden from an economic and health-related quality of life perspective. Moreover, growing evidence links NAFLD to common mental health disorders including depression, anxiety, and stress. In this context, recent clinical and research attention further focuses on potential additional problems faced by patients with NAFLD, such as perceived stigma, lack of awareness regarding the condition, and possible feelings of loneliness and isolation that might emerge from unmet support needs. To date, despite a wealth of literature on NAFLD, management of the condition remains challenging and not straightforward, with most cases in primary care being treated with lifestyle modification on top of any other comorbidity treatment. However, for many patients with NAFLD, weight loss is hard to accomplish and/or sustain (e.g., patients may lack the skills, confidence, and motivation required to adhere to dietary changes, and/or may have problems limiting opportunities for increased physical activity). Therefore, tailored interventions which are manageable from the perspective of the individual patient with NAFLD could glean greater results. Accordingly, although there is a lack of research exploring the potential benefits of person-centered and compassion-based approaches to the management of NAFLD, in the present review, we draw on evidence from methods utilized in the treatment of other chronic conditions in postulating the view that such approaches might prove beneficial in the future management of NAFLD.","PeriodicalId":74083,"journal":{"name":"Livers","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44499318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
LiversPub Date : 2023-08-19DOI: 10.3390/livers3030030
R. Teschke, G. Danan
{"title":"Idiosyncratic DILI and RUCAM under One Hat: The Global View","authors":"R. Teschke, G. Danan","doi":"10.3390/livers3030030","DOIUrl":"https://doi.org/10.3390/livers3030030","url":null,"abstract":"Drugs are prescribed worldwide to treat diseases but with the risk of idiosyncratic drug-induced liver injury (iDILI). The most important difficulty is how best to establish causality. Based on strong evidence and principles of artificial intelligence (AI) to solve complex processes through quantitative algorithms using scored elements, progress was achieved with the Roussel Uclaf Causality Assessment Method (RUCAM) in its original and updated versions, often viewed now as the gold standard. As a highly appreciated diagnostic algorithm, the RUCAM is in global use with around 100,000 iDILI cases published worldwide using RUCAM to assess causality, largely outperforming any other specific causality assessment tool in terms of case numbers. Consequently, the RUCAM helps to establish a list of top-ranking drugs worldwide implicated in iDILI and to describe clinical and mechanistic features of iDILI caused by various drugs. In addition, the RUCAM was recently applied in iDILI cases of patients treated for coronavirus disease 2019 (COVID-19) infections or cancer patients treated with immune checkpoint inhibitors (ICIs), as well as in the search for new treatment options with conventional drugs in iDILI. Analyses of RUCAM-based iDILI cases are helpful to support pathogenetic steps like immune reactions, genetic predisposition as evidenced by human leucocyte antigens (HLA) genotypes for selected drugs, and the role of the gut microbiome. To achieve consistency in data collection, analysis, and specific clinical and pathogenetic presentation, researchers, regulatory agencies, and pharmaceutical firms should place iDILI and the updated RUCAM as the causality tool under one and the same hat in review articles and clinical guidelines for the diagnosis and treatment of iDILI.","PeriodicalId":74083,"journal":{"name":"Livers","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42122688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
LiversPub Date : 2023-08-15DOI: 10.3390/livers3030029
Yankai Wen
{"title":"The Role of Immune Cells in Liver Regeneration","authors":"Yankai Wen","doi":"10.3390/livers3030029","DOIUrl":"https://doi.org/10.3390/livers3030029","url":null,"abstract":"The liver is the only organ that can regenerate and regain its original tissue-to-body weight ratio within a short period of time after tissue loss. Insufficient liver regeneration in patients after partial hepatectomy or liver transplantation with partial liver grafts often leads to post-hepatectomy liver failure or small-for-size syndrome, respectively. Enhancing liver regeneration after liver injury might improve outcomes and increase patient survival. Liver regeneration comprises hepatocyte proliferation, and hepatic progenitor cell expansion and differentiation into hepatocytes. The immune system is intensively involved in liver regeneration. The current review provides a comprehensive overview of the diverse roles played by immune cells in liver regeneration. Macrophages, neutrophils, eosinophils, basophils, mast cells, platelets, dendritic cells, type 1 innate lymphoid cells, B cells, and T cells are implicated in promoting liver regeneration, while natural killer cells and overactivated natural killer T cells are supposed to inhibit hepatocyte proliferation. We also highlight the predominant underlying mechanisms mediated by immune cells, which may contribute to the development of novel strategies for promoting liver regeneration in patients with liver diseases.","PeriodicalId":74083,"journal":{"name":"Livers","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45004272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
LiversPub Date : 2023-08-04DOI: 10.3390/livers3030028
Tong Liu, Yasmina Chouik, F. Lebossé, W. Khamri
{"title":"Dysfunctions of Circulating Adaptive Immune Cells in End-Stage Liver Disease","authors":"Tong Liu, Yasmina Chouik, F. Lebossé, W. Khamri","doi":"10.3390/livers3030028","DOIUrl":"https://doi.org/10.3390/livers3030028","url":null,"abstract":"End-stage liver disease (ESLD) from acute liver failure to compensated advanced chronic liver disease and decompensated cirrhosis at different stages (chronic decompensation, acute decompensation with or without acute-on-chronic liver failure) has high disease severity and poor patient outcome. Infection is a common complication in patients with ESLD and it is associated with a high mortality rate. Multiple mechanisms are involved in this marked susceptibility to infections, noticeably the inadequate immune response known as immune paresis, as part of cirrhosis-associated immune dysfunction (CAID). Specifically in the adaptive immune arm, lymphocyte impairments—including inadequate activation, reduced ability to secrete effector molecules and enhanced immune suppressive phenotypes—result in compromised systemic immune responses and increased risk of infections. This review summarises current knowledge of alterations in adaptive immune responsiveness and their underlying mechanisms in ESLD. Understanding these mechanisms is of crucial importance in the identification of potential therapeutic targets and applications of targeted treatments beyond antimicrobials, such as immunotherapy.","PeriodicalId":74083,"journal":{"name":"Livers","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41606977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}