Journal Description
Livers
Livers
is an international, peer-reviewed, open access journal on liver science published quarterly online by MDPI.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, EBSCO, and other databases.
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 22 days after submission; acceptance to publication is undertaken in 8.8 days (median values for papers published in this journal in the second half of 2023).
- Recognition of Reviewers: APC discount vouchers, optional signed peer review, and reviewer names published annually in the journal.
Latest Articles
Artificial Intelligence, Machine Learning, and Deep Learning in the Diagnosis and Management of Hepatocellular Carcinoma
Livers 2024, 4(1), 36-50; https://doi.org/10.3390/livers4010004 - 09 Jan 2024
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Artificial Intelligence (AI) can be a useful tool in the management of disease processes such as hepatocellular carcinoma (HCC) as treatment decisions are often complex and multifaceted. AI applications in medicine are expanding with the ongoing advances in AI including more sophisticated machine
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Artificial Intelligence (AI) can be a useful tool in the management of disease processes such as hepatocellular carcinoma (HCC) as treatment decisions are often complex and multifaceted. AI applications in medicine are expanding with the ongoing advances in AI including more sophisticated machine learning and deep learning processes. In preliminary studies, AI algorithms have demonstrated superiority in predicting the development of HCC compared with standard models. Radiomics, a quantitative method used to extract features from medical imaging, has been applied to numerous liver imaging modalities to aid in the diagnosis and prognostication of HCC. Deep learning methodologies can help us to identify patients at higher likelihood of disease progression and improve risk stratification. AI applications have expanded into the field of surgery as models not only help us to predict surgical outcomes but AI methodologies are also used intra-operatively, in real time, to help us to define anatomic structures and aid in the resection of complex lesions. In this review, we discuss promising applications of AI in the management of HCC. While further clinical validation is warranted to improve generalizability through the inclusion of larger and more diverse populations, AI is expected to play a central role in assisting clinicians with the management of complex disease processes such as HCC.
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Open AccessCommunication
Chronic Hepatitis B: A Summarized Anecdote of Complexities in Natural History, Treatment, and Complications
Livers 2024, 4(1), 31-35; https://doi.org/10.3390/livers4010003 - 29 Dec 2023
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Chronic hepatitis B is still a disease process that affects millions around the world. Serologies used to diagnose and follow the progression (or resolution) of the disease can be confusing for clinicians. Further, throughout years of treatment, there may be nuances in presentation
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Chronic hepatitis B is still a disease process that affects millions around the world. Serologies used to diagnose and follow the progression (or resolution) of the disease can be confusing for clinicians. Further, throughout years of treatment, there may be nuances in presentation that complicate management even further. In this short communication, we highlight six themes in response to treatment and outcomes, including complications. We have the unique perspective of following many patients over extended periods of time at our institution, which has brought these themes to life in order that they can be shared with other clinicians who may encounter similar situations.
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Open AccessArticle
Translocation of Adenosine A2B Receptor to Mitochondria Influences Cytochrome P450 2E1 Activity after Acetaminophen Overdose
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Livers 2024, 4(1), 15-30; https://doi.org/10.3390/livers4010002 - 26 Dec 2023
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The adenosine A2B receptor (A2BAR) is a member of a family of G-protein coupled receptors (GPCRs), which has a low affinity for adenosine and is now implicated in several pathophysiological conditions. We have demonstrated the beneficial effects of A2BAR activation in enhancing recovery
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The adenosine A2B receptor (A2BAR) is a member of a family of G-protein coupled receptors (GPCRs), which has a low affinity for adenosine and is now implicated in several pathophysiological conditions. We have demonstrated the beneficial effects of A2BAR activation in enhancing recovery after acute liver injury induced by an acetaminophen (APAP) overdose. While receptor trafficking within the cell is recognized to play a role in GPCR signaling, its role in the mediation of A2BAR effects in the context of APAP-induced liver injury is not well understood. This was investigated here, where C57BL/6J mice were subjected to an APAP overdose (300 mg/kg), and the temporal course of A2BAR intracellular localization was examined. The impact of A2BAR activation or inhibition on trafficking was examined by utilizing the A2BAR agonist BAY 60-6583 or antagonist PSB 603. The modulation of A2BAR trafficking via APAP-induced cell signaling was explored by using 4-methylpyrazole (4MP), an inhibitor of Cyp2E1 and JNK activation. Our results indicate that APAP overdose induced the translocation of A2BAR to mitochondria, which was prevented via 4MP treatment. Furthermore, we demonstrated that A2BAR is localized on the mitochondrial outer membrane and interacts with progesterone receptor membrane component 1 (PGRMC1). While the activation of A2BAR enhanced mitochondrial localization, its inhibition decreased PGRMC1 mitochondria levels and blunted mitochondrial Cyp2E1 activity. Thus, our data reveal a hitherto unrecognized consequence of A2BAR trafficking to mitochondria and its interaction with PGRMC1, which regulates mitochondrial Cyp2E1 activity and modulates APAP-induced liver injury.
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Open AccessReview
The Pivotal Role of the Membrane-Bound O-Acyltransferase Domain Containing 7 in Non-Alcoholic Fatty Liver Disease
Livers 2024, 4(1), 1-14; https://doi.org/10.3390/livers4010001 - 20 Dec 2023
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Non-alcoholic fatty liver disease (NAFLD) is a common and prevalent disorder affecting 25 percent of the adults in the United States and 32 percent of adults globally. It is one of the common causes of chronic liver disease characterized by steatosis, which can
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Non-alcoholic fatty liver disease (NAFLD) is a common and prevalent disorder affecting 25 percent of the adults in the United States and 32 percent of adults globally. It is one of the common causes of chronic liver disease characterized by steatosis, which can lead to inflammation, fibrosis, and cirrhosis. NAFLD is strongly associated with obesity and insulin resistance. Multiple genetic variants have been consistently found to be associated with NAFLD; one of them is found in the TMC4-MBOAT7 loci. One variant (rs641738 C>T) within MBOAT7 encoding lysophosphatidyl inositol acyltransferase increases the risk for NAFLD development and triggers hepatic inflammation by regulating arachidonic acid levels. This review provides an overview of the MBOAT7 gene, pathogenesis of NAFLD, understanding the regulation of MBOAT7 and mechanistic link between MBOAT7 and NAFLD. It further summarizes pathophysiologically relevant in vivo and in vitro studies on MBOAT7 and challenges in treating complex NAFLD with recent progress made in the treatment of NAFLD. As such, this review provides useful information on MBOAT7 and NAFLD interrelation, which has the potential of deciphering novel therapeutic targets rather than well-known genetic variants such as PNPLA3 and TM6SF2.
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(This article belongs to the Special Issue Liver Fibrosis: Mechanisms, Targets, Assessment and Treatment)
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Open AccessArticle
Exosome Shedding Is Concordant with Objective Treatment Response Rate and Stratifies Time to Progression in Treatment Naïve, Non-Resectable Hepatocellular Carcinoma
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Livers 2023, 3(4), 727-738; https://doi.org/10.3390/livers3040047 - 08 Dec 2023
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Translational strategies to characterize and monitor extracellular vesicles such as exosome (EX) shedding and the clinical impact of this data within hepatocellular carcinoma (HCC) remains unclear. In this study, EX shedding was assessed in early-stage HCC and evaluated as a stratification factor for
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Translational strategies to characterize and monitor extracellular vesicles such as exosome (EX) shedding and the clinical impact of this data within hepatocellular carcinoma (HCC) remains unclear. In this study, EX shedding was assessed in early-stage HCC and evaluated as a stratification factor for time to progression (TTP) following first-cycle liver-directed therapy (LDT). Plasma EXs were isolated from HCC patients undergoing LDT using ultracentrifugation. Purified EXs were stained using markers CD9 and CD63 and quantified using an ImageStreamX flow cytometer. Circulating EXs expressing CD9 were isolated at 10-fold higher levels compared to CD63. The intensity of CD9+ EX shedding following LDT was positively correlated with treatment response. High post-LDT CD9+ EX shedding stratified TTP risk with a 30% lower frequency of disease progression at 1 year following LDT. Post-LDT high CD9+ EX shedding was observed in 100% (10/10) of patients successfully bridged to liver transplantation while only 22% (2/9) of patients with tumor progression had high CD9+ EX shedding post-LDT. CD9+ EX shedding also stratified TTP risk within the first cycle objective response rate (ORR) group, identifying patients still at higher disease progression. EX shedding was concordant with imaging response rate, stratified TTP in early-stage HCC, and may have important implications for assessing post-LDT viable, biologically aggressive HCC.
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Open AccessReview
The Role of Normothermic Machine Perfusion in Extended Criteria Donor Grafts: A New Direction in Liver Graft Assessment and Preservation
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Livers 2023, 3(4), 709-726; https://doi.org/10.3390/livers3040046 - 01 Dec 2023
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Despite improvements in short-term and long-term outcomes of liver transplant patients, the discrepancy between the number of available livers and transplant candidates continues to increase. The use of expanded criteria donors is one strategy that can be used to address donor shortages. In
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Despite improvements in short-term and long-term outcomes of liver transplant patients, the discrepancy between the number of available livers and transplant candidates continues to increase. The use of expanded criteria donors is one strategy that can be used to address donor shortages. In recent years, preservation strategies such as normothermic machine perfusion (NMP) have been explored to improve the preservation of organs and test their viability before transplantation. We reviewed the recent literature and trials assessing the use of NMP in the setting of liver transplantation. Multiple feasibility trials have demonstrated the clinical prospect of NMP and proved its numerous advantages compared to conventional static cold storage. These advantages include preservation and viability assessment of high-risk donor allografts and grafts that would have otherwise been discarded. This review aims to address the topic of liver NMP in the setting of current and future applications in the setting of extended criteria donor grafts.
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Open AccessReview
Crosstalk between Lipids and Non-Alcoholic Fatty Liver Disease
Livers 2023, 3(4), 687-708; https://doi.org/10.3390/livers3040045 - 23 Nov 2023
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Non-alcoholic fatty liver disease (NAFLD), a complex liver disorder that can result in non-alcoholic steatohepatitis, cirrhosis, and liver cancer, is the accumulation of fat in the liver seen in people due to metabolic dysfunction. The pathophysiology of NAFLD is influenced by several variables,
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Non-alcoholic fatty liver disease (NAFLD), a complex liver disorder that can result in non-alcoholic steatohepatitis, cirrhosis, and liver cancer, is the accumulation of fat in the liver seen in people due to metabolic dysfunction. The pathophysiology of NAFLD is influenced by several variables, such as metabolic dysregulation, oxidative stress, inflammation, and genetic susceptibility. This illness seriously threatens global health because of its link to obesity, insulin resistance, type 2 diabetes, and other metabolic disorders. In recent years, lipid–NAFLD crosstalk has drawn a lot of interest. Through numerous methods, lipids have been connected to the onset and advancement of the illness. The connection between lipids and NAFLD is the main topic of the current review, along with the various therapeutic targets and currently available drugs. The importance of hepatic lipid metabolism in the progression of NAFLD is summarized with the latest results in the field.
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Open AccessArticle
Posterosuperior Segments of the Liver: Comparison of Short-Term Outcomes between Open and Minimally Invasive Surgery Performed by a Single Surgeon
Livers 2023, 3(4), 674-686; https://doi.org/10.3390/livers3040044 - 16 Nov 2023
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Laparoscopic posterosuperior liver segment resection is considered technically challenging. This is a retrospective single-center single-surgeon study. The aim of the present study is to investigate the short-term outcomes in a single institution between laparoscopic (LLR) and open (OLR) posterosuperior liver segments (PSSs) resections
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Laparoscopic posterosuperior liver segment resection is considered technically challenging. This is a retrospective single-center single-surgeon study. The aim of the present study is to investigate the short-term outcomes in a single institution between laparoscopic (LLR) and open (OLR) posterosuperior liver segments (PSSs) resections performed by a single surgeon at Parma University Hospital. The patients were divided into Group 1 (OLR) and Group 2 (LLR) and stratified in two different time settings according to the experience of the surgeon (2010–2015 and 2016–2021). A total 112 patients were included in the study. The 75.3% of OLR were performed in the first period, while 70.2% of LLR were carried out during the second period (2016–2021). The Iwate score was significantly (p < 0.001) higher in OLR group compared to the LLR group. Most of the advanced (77%) and expert (100%) LLRs were performed during the second period. LOS was shorter in LLR group comparing to OLR group (p < 0.001). The postoperative morbidity rate was similar in both groups (p > 0.05). The presence of liver cirrhosis and multiple lesions were identified as risk factors for severe postoperative complications. PSS-LLR has become much safer and more effective due to increasing surgeon’s expertise along with the implementation of cutting-edge technology and innovative surgical techniques.
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Open AccessArticle
The Computed Sinusoid
Livers 2023, 3(4), 657-673; https://doi.org/10.3390/livers3040043 - 11 Nov 2023
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Hepatic sinusoids are lined with thin endothelial cells with transcellular pores, termed fenestrations. These fenestrations are open channels that connect the sinusoidal lumen to the underlying Space of Disse (SoD) and the hepatocytes of the liver parenchyma. Fenestrations range from 0.05 to 0.35
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Hepatic sinusoids are lined with thin endothelial cells with transcellular pores, termed fenestrations. These fenestrations are open channels that connect the sinusoidal lumen to the underlying Space of Disse (SoD) and the hepatocytes of the liver parenchyma. Fenestrations range from 0.05 to 0.35 µm in diameter and cover 5–15% of the sinusoidal endothelial surface area, depending on their location along the sinusoids. The direct measurement of hemodynamic parameters, such as pressure and flow velocity, remains challenging within the narrow sinusoids. Such knowledge would increase our understanding of the physiology of the hepatic niche and possible implications in aging or diseases in which fenestrations are reduced or lost. Few simulations of liver blood flow focus on the level of the individual sinusoid, and fewer still include the transcellular pores (fenestrations) of the sinusoidal endothelium. Furthermore, none have included (i) a porosity gradient along the sinusoid wall, modeled using through-all pores rather than a porous medium, (ii) the presence of the SoD, or (iii) lymphatic drainage. Herein, computed fluid dynamics (CFD) simulations were performed using a numerical model with relevant anatomical characteristics (length, diameter, porosity, inlet/outlet pressure, and lymphatic outflow from the portal region of the SoD). The greatest contribution to luminal velocity magnitude and pressure was the overall shape of the vessel. Divergent-radius models yielded velocity magnitudes 1.5–2 times higher than constant-radius models, and pressures were 5–8% lower in the divergent-radius models compared to the constant-radius models. Porosity only modestly contributed to luminal pressure. The luminal velocity magnitude was largely unaffected by the presence or absence of lymphatic drainage. Velocity magnitudes through fenestrations were lower in higher-porosity models (20%) vs. lower-porosity models (5%) across all models (0.4–0.55-fold lower). Velocity magnitudes through the space of Disse were increased 3–4 times via the addition of lymphatic drainage to the models, while pressures were decreased by 6–12%. The flow velocity in the SoD was modified via differences in porosity, while the flow velocity in the lumens of the sinusoids was largely unaffected. The overall shape of the vessel is the single most important factor in the pressure flow behavior of the sinusoidal lumen. The flow rate over hepatocytes and the SoD is modestly affected by the distribution of porosity along the sinusoid and greatly affected by the lymphatic drainage, parameters that would be of interest for modeling the exchange of blood with the hepatic parenchyma.
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Open AccessReview
Advancements in Understanding and Treating NAFLD: A Comprehensive Review of Metabolic-Associated Fatty Liver Disease and Emerging Therapies
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Livers 2023, 3(4), 637-656; https://doi.org/10.3390/livers3040042 - 07 Nov 2023
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This paper provides a comprehensive review of the current understanding of non-alcoholic fatty liver disease (NAFLD) and its progression to non-alcoholic steatohepatitis (NASH), focusing on key factors influencing its pathogenesis and emerging therapeutic strategies. This review highlights the growing prevalence of NAFLD and
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This paper provides a comprehensive review of the current understanding of non-alcoholic fatty liver disease (NAFLD) and its progression to non-alcoholic steatohepatitis (NASH), focusing on key factors influencing its pathogenesis and emerging therapeutic strategies. This review highlights the growing prevalence of NAFLD and NASH, emphasizing their multifactorial nature. The manuscript identifies various contributors to NAFLD development, including genetic, dietary, and environmental factors, while examining the intricate interplay between these factors and their impact on hepatic lipid metabolism, inflammation, and insulin resistance. Genetic predisposition, dietary fat intake, and excessive fructose consumption are discussed as significant contributors to NAFLD progression. The article emphasizes the lack of a single therapeutic approach and underscores the need for combination strategies. Lifestyle interventions, particularly weight loss through diet and exercise, remain crucial, while pharmacological options like GLP-1 receptor agonists, obeticholic acid, lanifibranor, and resmetirom show promise but require further validation. Bariatric surgery and emerging endoscopic procedures offer potential in eligible patients. In sum, this article underscores the complexity of NAFLD and NASH, addresses key factors influencing pathogenesis, and discusses emerging therapies advocating for a multifaceted approach to this increasingly prevalent and clinically relevant condition.
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Open AccessReview
Hidden Dangers: Herbal and Dietary Supplement Induced Hepatotoxicity
Livers 2023, 3(4), 618-636; https://doi.org/10.3390/livers3040041 - 31 Oct 2023
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Herbal and dietary supplements represent a multi-billion-dollar industry reportedly used by over half of American adults. However, these products are not regulated by the Federal Drug Agency and contain a wide range of contaminants, leading to over 50,000 adverse events each year. This
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Herbal and dietary supplements represent a multi-billion-dollar industry reportedly used by over half of American adults. However, these products are not regulated by the Federal Drug Agency and contain a wide range of contaminants, leading to over 50,000 adverse events each year. This review aims to highlight the widespread use and current regulatory status of herbal and dietary supplements, identify the presentation and diagnostic dilemmas faced with liver injury, and discuss the most common agents implicated in herbal and dietary supplement hepatotoxicity.
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Open AccessReview
Therapeutics for Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD)
Livers 2023, 3(4), 597-617; https://doi.org/10.3390/livers3040040 - 28 Oct 2023
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Metabolic dysfunction associated fatty liver disease (MAFLD) has been recently recognized as a new global chronic liver disease entity with non-alcoholic fatty liver disease (NAFLD) associated with overweight/obesity or type 2 diabetes mellitus (T2DM) and evidence of metabolic dysregulation. Due to the rising
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Metabolic dysfunction associated fatty liver disease (MAFLD) has been recently recognized as a new global chronic liver disease entity with non-alcoholic fatty liver disease (NAFLD) associated with overweight/obesity or type 2 diabetes mellitus (T2DM) and evidence of metabolic dysregulation. Due to the rising rates of obesity and diabetes, MAFLD is considered a rapidly emerging chronic liver disease globally. Nearly 25–30% of the global population poses health issues due to MAFLD with a substantial economic burden to societies. Disease progression depends on the persistence of risk factors and etiological agents, from simple steatosis, hepatitis, fibrosis, to cirrhosis, and if untreated, leads to hepatocellular carcinoma. In this review article we summarize various risk and etiological factors, diagnostic techniques, and therapeutic evaluation of pharmacological agents developed for MAFLD. Effective pharmaceutical agents for the treatment of MAFLD (and NAFLD) are lacking, and research is ongoing to search for effective medications in this direction. Currently, pioglitazone is advised for MAFLD patients, whereas Vitamin E is advised for non-diabetic MAFLD patients with ≥F2 non-cirrhosis. Current approaches to disease management emphasize diet control, lifestyle changes, and weight loss. In this review, we summarized the pharmacological agents currently being developed and their current status to treat patients with MAFLD.
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Open AccessFeature PaperReview
The Evolution of Circulating Biomarkers for Use in Acetaminophen/Paracetamol-Induced Liver Injury in Humans: A Scoping Review
Livers 2023, 3(4), 569-596; https://doi.org/10.3390/livers3040039 - 27 Oct 2023
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Acetaminophen (APAP) is a widely used drug, but overdose can cause severe acute liver injury. The first reports of APAP hepatotoxicity in humans were published in 1966, shortly after the development of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) as the first biomarkers
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Acetaminophen (APAP) is a widely used drug, but overdose can cause severe acute liver injury. The first reports of APAP hepatotoxicity in humans were published in 1966, shortly after the development of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) as the first biomarkers of liver injury as opposed to liver function. Thus, the field of liver injury biomarkers has evolved alongside the growth in APAP hepatotoxicity incidence. Numerous biomarkers have been proposed for use in the management of APAP overdose patients in the intervening years. Here, we comprehensively review the development of these markers from the 1960s to the present day and briefly discuss possible future directions.
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(This article belongs to the Special Issue Recent Advances in Acetaminophen Hepatotoxicity)
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Open AccessCommunication
Pemafibrate Improves Alanine Aminotransferase Levels Independently of Its Lipid-Lowering Effect
Livers 2023, 3(4), 562-568; https://doi.org/10.3390/livers3040038 - 23 Oct 2023
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Aim: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. Pemafibrate, a selective peroxisome-proliferator-activated receptor α modulator (SPPARMα), has been reported to ameliorate liver function among patients with dyslipidemia. However, there are not many reports of the clinical
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Aim: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. Pemafibrate, a selective peroxisome-proliferator-activated receptor α modulator (SPPARMα), has been reported to ameliorate liver function among patients with dyslipidemia. However, there are not many reports of the clinical effects of pemafibrate. This study aims to summarize the experience of using pemafibrate and analyze the effects on liver function in patients with dyslipidemia. Methods: One hundred twelve cases of hyperlipidemia receiving pemafibrate 0.2 mg/day were retrospectively enrolled in this study. Age, gender, BMI, complications, concomitant medications, serum parameters (TG, HDL-C, LDL-C, AST, ALT, γGTP, ALP, platelets, M2BPGi, Cre, eGFR, HbA1c, blood glucose level at any time) were investigated and evaluated. Results: Pemafibrate administration significantly improved serum TG and HDL-C, but not in LDL-C. Serum AST, ALT, γGTP, and ALP were also significantly improved. The fib-4 index, a liver fibrosis score, did not significantly change, but M2-BPGi, an index of fibrosis, significantly decreased. No correlation was observed between each lipid parameter and ALT, and ALT decreased independently of the lipid parameters. Conclusions: As we expected, pemafibrate demonstrated a lipid-improving effect without adversely affecting hepatic and renal functions. An unexpected finding was the decrease in ALT that was independent of lipid parameters.
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Open AccessArticle
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
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Livers 2023, 3(4), 545-561; https://doi.org/10.3390/livers3040037 - 22 Sep 2023
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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
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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.
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Open AccessReview
Nutrition Therapy in Critically Ill Patients with Liver Disease: A Narrative Review
Livers 2023, 3(3), 529-544; https://doi.org/10.3390/livers3030036 - 21 Sep 2023
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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
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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.
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Open AccessReview
Hepatitis E Virus: Epidemiology, Clinical Aspects, and Its Significance as a Major Pregnancy Risk
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Livers 2023, 3(3), 507-528; https://doi.org/10.3390/livers3030035 - 15 Sep 2023
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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
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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.
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Open AccessArticle
Impact of IL-12B Genetic Variants on Antiviral Treatment Response among Hepatitis B Patients in Pakistan
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Livers 2023, 3(3), 494-506; https://doi.org/10.3390/livers3030034 - 12 Sep 2023
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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
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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.
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(This article belongs to the Special Issue Viral Hepatitis: Prevention, Infection, and Treatment)
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Open AccessReview
Relationship between Non-Alcoholic Fatty Liver Disease and Visceral Fat Measured by Imaging-Based Body Composition Analysis: A Systematic Review
Livers 2023, 3(3), 463-493; https://doi.org/10.3390/livers3030033 - 05 Sep 2023
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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
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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.
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Open AccessReview
Perspective on Quantitative Structure–Toxicity Relationship (QSTR) Models to Predict Hepatic Biotransformation of Xenobiotics
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Livers 2023, 3(3), 448-462; https://doi.org/10.3390/livers3030032 - 30 Aug 2023
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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
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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.
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