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.
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 36.3 days after submission; acceptance to publication is undertaken in 9.9 days (median values for papers published in this journal in the first half of 2023).
- Recognition of Reviewers: APC discount vouchers, optional signed peer review, and reviewer names published annually in the journal.
Latest Articles
Dysfunctions of Circulating Adaptive Immune Cells in End-Stage Liver Disease
Livers 2023, 3(3), 369-382; https://doi.org/10.3390/livers3030028 - 04 Aug 2023
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
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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.
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(This article belongs to the Special Issue The Role of Immune Cells in Acute and Chronic Liver Disease)
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Open AccessArticle
KIR Genotypes Impact Progression to Hepatocellular Carcinoma in Patients with Chronic Hepatitis C Infection
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Livers 2023, 3(3), 354-368; https://doi.org/10.3390/livers3030027 - 31 Jul 2023
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In Egypt, hepatocellular carcinoma (HCC) is the most prevalent cancer in men and the second most prevalent cancer in women. In addition, Egypt has one of the highest prevalences of hepatitis C infection in the world. The aim of the present work was
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In Egypt, hepatocellular carcinoma (HCC) is the most prevalent cancer in men and the second most prevalent cancer in women. In addition, Egypt has one of the highest prevalences of hepatitis C infection in the world. The aim of the present work was to study the potential role of the 16 KIR genes in the outcome of individuals with chronic hepatitis C virus (HCV) infection in Egypt. The study was carried out under an IRB-approved protocol. Sequence-Specific-Primer-PCR (SSP-PCR) was used for KIR genotyping of germline DNA extracted from peripheral blood leukocytes or from the non-tumor liver of 83 HCC patients, 100 patients with chronic HCV infection without HCC, and 120 matched healthy controls. Out of the 83 HCC patients, only 7 (8.4%) were treated by interferon and/or interferon Ribavirin combination, while for the remaining patients 50 (60.2%) received no prior HCV therapy and 26 (31.3%) were treated with direct-acting antiviral (DAA). Our results showed that KIR haplotype AA that contains more inhibitory KIR genes and fewer activating genes was observed with a significantly lower frequency in HCC patients (6/83, 7.2%) compared to chronic HCV (27/100, 27.0%) (p = 0.0005, OR = 0.21 [0.08–0.53]) and healthy controls (29/119, 24.4%) (p = 0.001, OR = 0.24 [0.09–0.61]). In addition, the frequency of genotype 6 (G6) which contains all the KIR genes was significantly high in the HCC patients (16/83, 19.3%) compared to chronic HCV (8/100, 8.0%) (p = 0.02, OR = 2.7 [1.11–6.79]) and healthy controls (8/119, 6.7%) (p = 0.006, OR = 3.31 [1.35–8.16]). Activating KIR genes 2DS1 and 3DS1 were significantly higher in HCC patients (48/83, 57.83% and 45/83, 54.22%) compared to the chronic HCV patients (36/100, 36% and 34/100, 34%), p = 0.028, 0.027, respectively. Our results are contrary to a prior work on HCC from patients with HCV who were mostly treated by interferon-based therapies. In conclusion, KIR haplotype AA has an important role in host defense against HCC progression especially in patients treated by DAA, suggesting an important role of the KIR genotype status on the outcome of chronic HCV infection.
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Open AccessCase Report
Can Hepatitis B Virus (HBV) Reactivation Result from a Mild COVID-19 Infection?
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Livers 2023, 3(3), 347-353; https://doi.org/10.3390/livers3030026 - 25 Jul 2023
Abstract
Hepatitis B virus reactivation (HBVr) is a well-described result of immunosuppressive therapy initiation in various diseases, with the dose and duration of treatment being the main factors determining the probability for reactivation. Such cases have also been described in COVID-19 patients treated with
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Hepatitis B virus reactivation (HBVr) is a well-described result of immunosuppressive therapy initiation in various diseases, with the dose and duration of treatment being the main factors determining the probability for reactivation. Such cases have also been described in COVID-19 patients treated with immunosuppressive therapies. Nevertheless, cases of COVID-19 infection that led to HBVr with no concurrent immunosuppressive treatment or any other related cause have also been reported. By that observation, we present a patient followed for a period spanning 20 years with HBeAg negative chronic HBV infection and non-detectable HBV DNA who, after a mild COVID-19 infection treated only with low-dose and short-duration-inhaled corticosteroids (ICS), developed elevated AST and ALT as well as elevated HBV DNA levels. Other etiologies of abnormal liver biochemistries during the diagnostic workout were excluded; thus, the diagnosis of HBV reactivation was established. Treatment with entecavir was initiated, leading to the normalization of AST and ALT levels and a decreasing trend of HBV DNA levels. Since other causes of reactivation were excluded, and the ICS dose and duration were found baring only a very low risk (<1%) for HBVr, COVID-19 infection could be considered the most probable cause of reactivation, hence underlining the need for the close monitoring of those patients.
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Open AccessArticle
Transcriptomics of Congenital Hepatic Fibrosis in Autosomal Recessive Polycystic Kidney Disease Using PCK Rats
Livers 2023, 3(3), 331-346; https://doi.org/10.3390/livers3030025 - 21 Jul 2023
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Congenital hepatic fibrosis/Autosomal recessive polycystic kidney disease (CHF/ARPKD) is an inherited neonatal disease induced by mutations in the PKHD1 gene and characterized by cysts and robust pericystic fibrosis in the liver and kidneys. The PCK rat is an excellent animal model that carries
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Congenital hepatic fibrosis/Autosomal recessive polycystic kidney disease (CHF/ARPKD) is an inherited neonatal disease induced by mutations in the PKHD1 gene and characterized by cysts and robust pericystic fibrosis in the liver and kidneys. The PCK rat is an excellent animal model that carries a Pkhd1 mutation and exhibits similar pathophysiology. We performed RNA-Seq analysis on liver samples from PCK rats over a time course of postnatal day (PND) 15, 20, 30, and 90 using age-matched Sprague Dawley (SD) rats as controls to characterize molecular mechanisms of CHF/ARPKD pathogenesis. A comprehensive gene expression analysis identified 1298 differentially expressed genes (DEGs) between PCK and SD rats. The genes overexpressed in the PCK rats at PND30 and 90 were involved cell migration (e.g., Lamc2, Tgfb2, and Plet1), cell adhesion (e.g., Spp1, Adgrg1, and Cd44), and wound healing (e.g., Plat, Celsr1, Tpm1). Connective tissue growth factor (Ctgf) and platelet-derived growth factor (Pdgfb), two genes associated with fibrosis, were upregulated in PCK rats at all time points. Genes associated with MHC class I molecules (e.g., RT1-A2) or involved in ribosome assembly (e.g., Pes1) were significantly downregulated in PCK rats. Upstream regulator analysis showed activation of proteins involved tissue growth (MTPN) inflammation (STAT family members), chromatin remodeling (BRG1), reduction in fibrosis (SMAD7), and inhibition of proteins involved in hepatic differentiation (HNF4α). Immunofluorescence staining revealed that cyst wall epithelium cells also express hepatic progenitor cell markers. The increase in mRNAs of four top upregulated genes, including Reg3b, Aoc1, Tm4sf20, and Cdx2, was confirmed at the protein level using immunohistochemistry. In conclusion, these studies indicate that a combination of increased inflammation, cell migration, wound healing, decreased antifibrotic gene expression, and inhibition of hepatic function are the major underlying pathogenic mechanisms in CHF/ARPKD.
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Open AccessCommunication
The Long Game: A Functional Cure Is Possible with Nucleoside Analogues and the Tincture of Time
Livers 2023, 3(3), 325-330; https://doi.org/10.3390/livers3030024 - 04 Jul 2023
Abstract
Chronic hepatitis B is still prevalent globally. Many patients are treated for many years with nucleos(t)ide analogues to prevent the virus from actively replicating. However, although it typically requires consecutive treatment for more than 10 years, patients can achieve a functional cure from
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Chronic hepatitis B is still prevalent globally. Many patients are treated for many years with nucleos(t)ide analogues to prevent the virus from actively replicating. However, although it typically requires consecutive treatment for more than 10 years, patients can achieve a functional cure from this virus. This case series presents details of functional cures in patients who received varying nucleos(t)ide therapies for an average of 15.3 years before losses of hepatitis B surface antigen and viral load were observed. It is imperative to understand that abbreviating therapy once a functional cure is achieved may be a possibility in treating patients in order to limit the associated costs and side effects of an otherwise lifelong therapy until other cure drugs are approved.
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Open AccessEditorial
Special Issue “Liver Fibrosis: Mechanisms, Targets, Assessment and Treatment”
Livers 2023, 3(3), 322-324; https://doi.org/10.3390/livers3030023 - 27 Jun 2023
Abstract
Fibrosis is a double-edged sword [...]
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(This article belongs to the Special Issue Liver Fibrosis: Mechanisms, Targets, Assessment and Treatment)
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Open AccessArticle
The Role of Cytochrome P450 3A4-Mediated Metabolism in Sorafenib and Lapatinib Hepatotoxicity
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Livers 2023, 3(2), 310-321; https://doi.org/10.3390/livers3020022 - 19 Jun 2023
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Tyrosine kinase inhibitors (TKIs) are increasingly popular drugs used to treat more than a dozen different diseases including some forms of cancer. Despite having fewer adverse effects than traditional chemotherapies, they are not without risks. Liver injury is a particular concern. Of the
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Tyrosine kinase inhibitors (TKIs) are increasingly popular drugs used to treat more than a dozen different diseases including some forms of cancer. Despite having fewer adverse effects than traditional chemotherapies, they are not without risks. Liver injury is a particular concern. Of the FDA-approved TKIs, approximately 40% cause hepatotoxicity. However, little is known about the underlying pathophysiology. The leading hypothesis is that TKIs are converted by cytochrome P450 3A4 (CYP3A4) to reactive metabolites that damage proteins. Indeed, there is strong evidence for this bioactivation of TKIs in in vitro reactions. However, the actual toxic effects are underexplored. Here, we measured the cytotoxicity of several TKIs in primary mouse hepatocytes, HepaRG cells and HepG2 cells with and without CYP3A4 modulation. To our surprise, the data indicate that CYP3A4 increases resistance to sorafenib and lapatinib hepatotoxicity. The results have implications for the mechanism of toxicity of these drugs in patients and underline the importance of selecting an appropriate experimental model.
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Open AccessReview
Regeneration and Recovery after Acetaminophen Hepatotoxicity
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Livers 2023, 3(2), 300-309; https://doi.org/10.3390/livers3020021 - 09 Jun 2023
Abstract
Liver regeneration is a compensatory response to tissue injury and loss. It is known that liver regeneration plays a crucial role in recovery following acetaminophen (APAP)-induced hepatotoxicity, which is the major cause of acute liver failure (ALF) in the US. Regeneration increases proportional
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Liver regeneration is a compensatory response to tissue injury and loss. It is known that liver regeneration plays a crucial role in recovery following acetaminophen (APAP)-induced hepatotoxicity, which is the major cause of acute liver failure (ALF) in the US. Regeneration increases proportional to the extent of liver injury upon APAP overdose, ultimately leading to regression of injury and spontaneous recovery in most cases. However, severe APAP overdose results in impaired liver regeneration and unchecked progression of liver injury, leading to failed recovery and mortality. Inter-communication between various cell types in the liver is important for effective regenerative response following APAP hepatotoxicity. Various non-parenchymal cells such macrophages, stellate cells, and endothelial cells produce mediators crucial for proliferation of hepatocytes. Liver regeneration is orchestrated by synchronized actions of several proliferative signaling pathways involving numerous kinases, nuclear receptors, transcription factors, transcriptional co-activators, which are activated by cytokines, growth factors, and endobiotics. Overt activation of anti-proliferative signaling pathways causes cell-cycle arrest and impaired liver regeneration after severe APAP overdose. Stimulating liver regeneration by activating proliferating signaling and suppressing anti-proliferative signaling in liver can prove to be important in developing novel therapeutics for APAP-induced ALF.
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(This article belongs to the Special Issue Recent Advances in Acetaminophen Hepatotoxicity)
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Open AccessBook Review
Book Review: Weiskirchen, R.; Friedman, S.L. Hepatic Stellate Cells: Methods and Protocols, 1st Ed.; Weiskirchen, R., Friedman, S.L., Eds.; Methods in Molecular Biology 2669; Humana Press: New York, NY, USA, 2023; ISBN 978-1-07-163206-2; eISBN: 978-1-0716-3207-9
Livers 2023, 3(2), 293-299; https://doi.org/10.3390/livers3020020 - 29 May 2023
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Hepatic stellate cells (HSCs) are a liver-specific mesenchymal cell type located in the Dissé space between hepatocytes and sinusoidal endothelial cells [...]
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Open AccessArticle
Expression of Bone Morphogenetic Protein 14 in Liver Disease and Cancer
Livers 2023, 3(2), 282-292; https://doi.org/10.3390/livers3020019 - 25 May 2023
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The activation of hepatic stellate cells (HSCs) is the key event of hepatic fibrosis. Furthermore, activated HSCs also play an important role in the progression of hepatocellular cancer (HCC). Bone morphogenetic protein 14 (BMP14) is a member of the TGF-β/BMP superfamily. So far,
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The activation of hepatic stellate cells (HSCs) is the key event of hepatic fibrosis. Furthermore, activated HSCs also play an important role in the progression of hepatocellular cancer (HCC). Bone morphogenetic protein 14 (BMP14) is a member of the TGF-β/BMP superfamily. So far, most studies have analyzed BMP14 in the context of bone and cartilage formation and homeostasis. The aim of this study was to assess the expression and function of BMP14 in liver fibrosis and HCC. The BMP14 expression increased during the in vitro activation of primary human HSCs and also in mouse models of liver fibrosis. In human HCC, as well as non-tumorous liver tissues, there was a significant correlation between the expression of BMP14 and alpha-smooth-muscle actin (α-SMA), an established marker for HSC activation. RNAi-mediated BMP14 suppression in activated HSCs resulted in the reduced expression of the transcription factors inhibitor of differentiation 1 (ID1) and ID2, known targets of BMP signaling. Interestingly, α-SMA and collagen expression was also reduced in BMP14-depleted cells, while treatment with recombinant BMP14 induced ID1, ID2, α-SMA and collagen expression. In human HCC cell lines, treatment with recombinant BMP14 induced proliferation, migratory activity and colony formation. In summary, our data indicate activated HSCs as a major cellular source of enhanced BMP14 expression in fibrotic liver disease and HCC, and show that BMP14 exhibits pro-fibrogenic as well as pro-tumorigenic effects. Future analyses will reveal the potential of this soluble growth factor as a therapeutic target or prognostic marker for the progression of fibrosis and HCC in patients with chronic liver disease.
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Open AccessArticle
Prevalence and Trends in Hepatitis B & C Virus among Blood Donors in Pakistan: A Regional Transfusion Center Study
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Livers 2023, 3(2), 271-281; https://doi.org/10.3390/livers3020018 - 17 May 2023
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Around 118.5 million blood donations are collected annually to save precious lives. The donated blood may also be associated with blood-borne infections. With around 247 million population, Pakistan is an endemic country for viral hepatitis, and there is a high risk of having
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Around 118.5 million blood donations are collected annually to save precious lives. The donated blood may also be associated with blood-borne infections. With around 247 million population, Pakistan is an endemic country for viral hepatitis, and there is a high risk of having asymptomatic blood donors among healthy donors. Viral hepatitis is 2.5% prevalent in the general population, and blood donation and its screening have become grave health concerns for Pakistani health authorities. Asymptomatic viral hepatitis needs screening to rule out subliminally diseased individuals, as recommended by the World Health Organization. Knowing the prevalence of the transfusion transmissible infectious (TTIs) agents in healthy blood donors helps assess the disease burden in any population, boosts treatment rates, and precludes dreaded complications in the affected people. The objective of the current study was to determine the prevalence and trends of significant TTIs among blood donors visiting the Armed Forces Institute of Transfusion (AFIT), Rawalpindi, Pakistan. A total of 15,405 blood donors were screened for HBV, HCV, HIV, malaria, and syphilis during this cross-sectional descriptive study. Most donors had an O-positive blood group; AB-negative donors were only 0.7%. Out of the study population, we reported 1.06% HBV, 0.54% HCV, 0.19% HIV, and 0.31% syphilis-positive asymptomatic blood donors. However, no blood donor was found positive for malaria. The Punjab province was reported as the most burdened for TTIs, and youngsters aged 18–27 years were mainly positive, indicating the need to conduct national-level awareness campaigns about TTIs. The stakeholders need to strengthen the blood collection guidelines, and effective performance should be strictly monitored through internal and external audits considering the aim of reaching non-infectious blood products.
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Open AccessArticle
Effect of Bergamot Leaves (Citrus bergamia) in the Crosstalk between Adipose Tissue and Liver of Diet-Induced Obese Rats
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Livers 2023, 3(2), 258-270; https://doi.org/10.3390/livers3020017 - 11 May 2023
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The excessive consumption of diets rich in sugar and fat is associated with metabolic manifestations involving adipose tissue and the liver. Bergamot, due to its antioxidant and anti-inflammatory properties, has been used to treat metabolic disorders. This work aimed to verify the effect
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The excessive consumption of diets rich in sugar and fat is associated with metabolic manifestations involving adipose tissue and the liver. Bergamot, due to its antioxidant and anti-inflammatory properties, has been used to treat metabolic disorders. This work aimed to verify the effect of Bergamot leaves extract (BLE) on the crosstalk in the adipose tissue–liver axis of obese rats. For 20 weeks, Wistar rats were distributed into two groups: control (Control) and high sugar–fat (HSF) diet groups. Afterwards, the animals were redistributed into three groups for 10 weeks: control diet + vehicle (Control, n = 08), HSF + vehicle (HSF, n = 08), and HSF + BLE (HSF + BLE, n = 08). The BLE was carried out daily by gavage (50 mg/kg). The HSF group presented obesity, hyperglycemia, hypertriglyceridemia, insulin resistance, hepatic microvesicular steatosis, higher inflammation and oxidative stress in the liver and adipose tissue. In comparison to the HSF group, HSF + BLE animals showed protection by reducing the triglyceride levels, insulin resistance, inflammation and oxidative stress in hepatic and adipose tissues. BLE acted on the inflammation and oxidative stress in the adipose tissue–liver axis in obese rats when compared to the HSF group, which may have reflected on the improvement of insulin resistance and dyslipidemia.
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Open AccessReview
Peritoneal Immunity in Liver Disease
Livers 2023, 3(2), 240-257; https://doi.org/10.3390/livers3020016 - 26 Apr 2023
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The peritoneum represents a confined microenvironment that has an emerging role as a distinct immunological compartment. In health, this niche is mainly populated by a heterogenous group of macrophages and T lymphocytes but also Natural Killer cells and B lymphocytes. Together they are
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The peritoneum represents a confined microenvironment that has an emerging role as a distinct immunological compartment. In health, this niche is mainly populated by a heterogenous group of macrophages and T lymphocytes but also Natural Killer cells and B lymphocytes. Together they are crucial for immunological surveillance, clearance of infection and resolution of inflammation. Development of ascites is a defining feature of decompensated liver cirrhosis, and spontaneous bacterial peritonitis is the most frequent bacterial infection occurring in this patient group. Recent studies of ascitic fluid have revealed quantitative, phenotypic and functional differences in both innate and adaptive immune cells compared to the healthy state. This review summarises current knowledge of these alterations and explores how the peritoneum in chronic liver disease is simultaneously an immunologically compromised site and yet capable of provoking an intense inflammatory response. A better understanding of this might enable identification of new therapeutic targets aimed to rebalance the peritoneal immunity and reduce the reliance on antimicrobials in an era of increasing antimicrobial resistance.
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(This article belongs to the Special Issue The Role of Immune Cells in Acute and Chronic Liver Disease)
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Open AccessCommunication
Chronicles of HBV and the Road to HBV Cure
Livers 2023, 3(2), 232-239; https://doi.org/10.3390/livers3020015 - 20 Apr 2023
Abstract
Chronic hepatitis B remains a major public health concern and a leading cause of morbidity and mortality worldwide, specifically through its causative role in chronic liver disease and hepatocellular carcinoma. Worldwide, it affects up to 292 million people. In this paper, we review
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Chronic hepatitis B remains a major public health concern and a leading cause of morbidity and mortality worldwide, specifically through its causative role in chronic liver disease and hepatocellular carcinoma. Worldwide, it affects up to 292 million people. In this paper, we review the historic discovery of the hepatitis B virus and chronicle the significant advances in our understanding of the virus and its interactions with the human host to cause disease. We also overview advancements in therapies for hepatitis B virus and the current absence of curative therapies and highlight on-going therapeutic efforts in search of curative therapies to control transmission and eradicate hepatitis B virus.
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(This article belongs to the Special Issue Recent Advances in the Clinical Outcome of Chronic Hepatitis B Patients)
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Open AccessReview
Mitochondria in Acetaminophen-Induced Liver Injury and Recovery: A Concise Review
Livers 2023, 3(2), 219-231; https://doi.org/10.3390/livers3020014 - 10 Apr 2023
Abstract
Mitochondria are critical organelles responsible for the maintenance of cellular energy homeostasis. Thus, their dysfunction can have severe consequences in cells responsible for energy-intensive metabolic function, such as hepatocytes. Extensive research over the last decades have identified compromised mitochondrial function as a central
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Mitochondria are critical organelles responsible for the maintenance of cellular energy homeostasis. Thus, their dysfunction can have severe consequences in cells responsible for energy-intensive metabolic function, such as hepatocytes. Extensive research over the last decades have identified compromised mitochondrial function as a central feature in the pathophysiology of liver injury induced by an acetaminophen (APAP) overdose, the most common cause of acute liver failure in the United States. While hepatocyte mitochondrial oxidative and nitrosative stress coupled with induction of the mitochondrial permeability transition are well recognized after an APAP overdose, recent studies have revealed additional details about the organelle’s role in APAP pathophysiology. This concise review highlights these new advances, which establish the central role of the mitochondria in APAP pathophysiology, and places them in the context of earlier information in the literature. Adaptive alterations in mitochondrial morphology as well as the role of cellular iron in mitochondrial dysfunction and the organelle’s importance in liver recovery after APAP-induced injury will be discussed.
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(This article belongs to the Special Issue Recent Advances in Acetaminophen Hepatotoxicity)
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Open AccessReview
Principles of Nutritional Management in Patients with Liver Dysfunction—A Narrative Review
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Livers 2023, 3(2), 190-218; https://doi.org/10.3390/livers3020013 - 04 Apr 2023
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According to studies, the liver’s ability to perform its physiological functions in the body determines the diet of patients with liver diseases. Malnutrition results from the liver’s inability to metabolize nutrients as a result of chronic liver dysfunctions. Objectives: Reviewing the data about
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According to studies, the liver’s ability to perform its physiological functions in the body determines the diet of patients with liver diseases. Malnutrition results from the liver’s inability to metabolize nutrients as a result of chronic liver dysfunctions. Objectives: Reviewing the data about diets and dietary supplements that manage liver dysfunctions nutritionally. Results: Malnutrition is particularly prevalent in cirrhosis patients, according to clinical studies. Because malnutrition has a significant negative impact on morbidity, mortality, and quality of life, it is crucial to evaluate all cirrhosis patients, regardless of etiology or severity. A term of supplemental enteral nutrition may be suggested for patients who do not achieve their nutritional objectives. A detailed nutritional and exercise assessment will enable the development of an individualized treatment plan that includes dietary and exercise plans. The dietary treatment should outline daily calorie targets with a focus on high-quality protein and address any vitamin and micronutrient deficiencies, with a diet high in those nutrients or supplements. Conclusions: While there is evidence to support the use of particular restricted dietary plans and dietary supplements to manage liver diseases, these findings should be regarded as preliminary until they are confirmed in larger randomized controlled clinical trials.
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Open AccessReview
An Updated Review on Advances in Hydrogel-Based Nanoparticles for Liver Cancer Treatment
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Livers 2023, 3(2), 161-189; https://doi.org/10.3390/livers3020012 - 27 Mar 2023
Cited by 3
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More than 90% of all liver malignancies are hepatocellular carcinomas (HCCs), for which chemotherapy and immunotherapy are the ideal therapeutic choices. Hepatocellular carcinoma is descended from other liver diseases, such as viral hepatitis, alcoholism, and metabolic syndrome. Normal cells and tissues may suffer
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More than 90% of all liver malignancies are hepatocellular carcinomas (HCCs), for which chemotherapy and immunotherapy are the ideal therapeutic choices. Hepatocellular carcinoma is descended from other liver diseases, such as viral hepatitis, alcoholism, and metabolic syndrome. Normal cells and tissues may suffer damage from common forms of chemotherapy. In contrast to systemic chemotherapy, localized chemotherapy can reduce side effects by delivering a steady stream of chemotherapeutic drugs directly to the tumor site. This highlights the significance of controlled-release biodegradable hydrogels as drug delivery methods for chemotherapeutics. This review discusses using hydrogels as drug delivery systems for HCC and covers thermosensitive, pH-sensitive, photosensitive, dual-sensitive, and glutathione-responsive hydrogels. Compared to conventional systemic chemotherapy, hydrogel-based drug delivery methods are more effective in treating cancer.
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Open AccessReview
Unresectable Hepatocellular Carcinoma: A Review of New Advances with Focus on Targeted Therapy and Immunotherapy
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Livers 2023, 3(1), 121-160; https://doi.org/10.3390/livers3010011 - 13 Mar 2023
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With an expected incidence of more than 1 million cases by 2025, liver cancer remains a problem for world health. With over 90% of cases, hepatocellular carcinoma (HCC) is the most prevalent kind of liver cancer. In this review, we presented the range
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With an expected incidence of more than 1 million cases by 2025, liver cancer remains a problem for world health. With over 90% of cases, hepatocellular carcinoma (HCC) is the most prevalent kind of liver cancer. In this review, we presented the range of experimental therapeutics for patients with advanced HCC, the successes and failures of new treatments, areas for future development, the evaluation of dose-limiting toxicity in different drugs, and the safety profile in patients with liver dysfunction related to the underlying chronic liver disease. In addition to the unmet demand for biomarkers to guide treatment decisions and the burgeoning fields of immunotherapy and systemic therapy in hepatocellular carcinoma, the development of old and new drugs, including their failures and current advancements, has been reviewed. This review aims to evaluate the updated optimal clinical treatment of unresectable hepatocellular carcinomas in clinical practice, mainly through targeted therapy. Although surgical treatment can significantly enhance the survival probability of early and intermediate-stage patients, it is unsuitable for most HCC patients due to a lack of donors. Due to their severe toxicity, the few first-line anti-HCC drugs, such as sorafenib, are often reserved for advanced HCC patients for whom other therapies have failed. The second-line drugs are usually alternatives for patients with intolerance or resistance. Consequently, the ongoing growth of possible preclinical drugs and studies on miRNAs, lncRNAs, and numerous other signaling pathway targets for developing novel drugs may introduce additional treatment prospects for HCC.
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Open AccessArticle
Tempol Alters Antioxidant Enzyme Function, Modulates Multiple Genes Expression, and Ameliorates Hepatic and Renal Impairment in Carbon Tetrachloride (CCl4)-Intoxicated Rats
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Livers 2023, 3(1), 105-120; https://doi.org/10.3390/livers3010010 - 08 Mar 2023
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The purpose of this study was to determine the effect of the superoxide dismutase mimic compound “tempol” on liver and renal damage in Long Evans male rats administered with carbon tetrachloride (CCl4). Methods: The antioxidant enzyme activity and oxidative stress parameters
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The purpose of this study was to determine the effect of the superoxide dismutase mimic compound “tempol” on liver and renal damage in Long Evans male rats administered with carbon tetrachloride (CCl4). Methods: The antioxidant enzyme activity and oxidative stress parameters were investigated in the liver, kidney, and plasma tissues. Histological examination of the liver and kidney sections affirmed inflammatory cell infiltration, collagen deposition, and iron deposition. RT-PCR was also employed to evaluate the expression of oxidative stress and inflammatory genes. Results: The CCl4-administered rats exhibited increased plasma activities of ALT, AST, and ALP compared to the control rats. The tempol treatment in the CCl4-administered rats significantly lowered ALT, AST, and ALP enzyme activities compared to the CCl4 group. Oxidative stress parameters, such as the MDA, NO, and APOP levels in various tissues of the CCl4-administered rats, showed increased concentrations, whereas tempol significantly lowered the level of oxidative stress. Moreover, CCl4 administration decreased the antioxidant enzyme activities, which were further significantly restored by the tempol treatment. The control rats that underwent treatment with tempol did not present with any abnormality or toxicity. Furthermore, the tempol treatment in the CCl4-administered rats increased Nrf-2-HO-1-mediated gene expression and enhanced related antioxidant enzyme gene expressions. The tempol treatment in the CCl4-administered rats also decreased anti-inflammatory gene expressions in the liver. In histological sections of the liver, CCl4 increased inflammatory cell infiltration, collagen deposition, and iron deposition, which were reduced significantly due to the tempol treatment. Conclusion: The results of this investigation revealed that tempol could protect against liver and kidney damage in CCl4-administered rats by modulating antioxidant gene expressions and restoring antioxidant defense mechanisms.
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Open AccessArticle
Single Center Experience of Oral Vancomycin Therapy in Young Patients with Primary Sclerosing Cholangitis: A Case Series
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Livers 2023, 3(1), 93-104; https://doi.org/10.3390/livers3010009 - 06 Mar 2023
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There is no single proven therapy that prolongs hepatic transplant-free survival in patients with primary sclerosing cholangitis (PSC). Oral vancomycin (OV) has shown some benefit in small pediatric and adult series. We describe the effect of OV on pediatric onset PSC at our
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There is no single proven therapy that prolongs hepatic transplant-free survival in patients with primary sclerosing cholangitis (PSC). Oral vancomycin (OV) has shown some benefit in small pediatric and adult series. We describe the effect of OV on pediatric onset PSC at our tertiary hospital. This is a single-center, retrospective, descriptive case series involving patients (<21 years at diagnosis) with PSC on OV from 2001 till 2021. The therapy effect was assessed based on symptoms, biochemical labs, imaging and liver biopsy at six and twelve months, and then annually until therapy was discontinued. The inclusion criteria identified 17 patients. Baseline GGT (n = 17) was elevated among 88.2% which then normalized among 53.8% (n = 13) at six months and 55.6% (n = 9) at one year post-OV. Baseline ALT normalized in 58.8% (n = 17) at six months and 42.8% (n = 14) at one year. Imaging findings within one year of OV revealed improved/stable biliary findings among 66.7% (n = 8/12). No adverse events were reported. OV was associated with an improvement in bile duct injury marker (GGT) after at least six months of therapy, with no disease progression on imaging within one year of therapy.
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