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Livers, Volume 3, Issue 1 (March 2023) – 11 articles

Cover Story (view full-size image): Non-alcoholic fatty liver disease (NAFLD) is the most frequently occurring chronic liver disease. NAFLD reflects excess hepatic accumulation of fat in the absence of increased alcohol intake and due to its close association with obesity. In addition to its well-established link with the metabolic syndrome and increased risk for cardiovascular disease, NAFLD has also been associated with certain mental health issues. As such, this review aimed to assess such potential problems faced by patients with NAFLD and to explore the possibility of unmet support needs which could lead to perceived social isolation. Moreover, the importance of a compassionate approach towards such patients is discussed, together with potential coping strategies. Future research directions and the need for a multidisciplinary approach are also highlighted. View this paper
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40 pages, 2224 KiB  
Review
Unresectable Hepatocellular Carcinoma: A Review of New Advances with Focus on Targeted Therapy and Immunotherapy
by Bahareh Farasati Far, Dorsa Rabie, Parisa Hemati, Parastoo Fooladpanjeh, Neda Faal Hamedanchi, Nima Broomand Lomer, Arian Karimi Rouzbahani and Mohammad Reza Naimi-Jamal
Livers 2023, 3(1), 121-160; https://doi.org/10.3390/livers3010011 - 13 Mar 2023
Cited by 2 | Viewed by 4627
Abstract
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 [...] Read more.
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. Full article
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16 pages, 12336 KiB  
Article
Tempol Alters Antioxidant Enzyme Function, Modulates Multiple Genes Expression, and Ameliorates Hepatic and Renal Impairment in Carbon Tetrachloride (CCl4)-Intoxicated Rats
by Ishrat Jahan, Md. Didarul Islam, Sumaia Sarif, Israt Jahan Amena, Asif Ul Haque Shuvo, Noushin Akter, Faizul Islam Chowdhury, Raushanara Akter, Iqbal Ahmed, Ferdous Khan, Nusrat Subhan and Md. Ashraful Alam
Livers 2023, 3(1), 105-120; https://doi.org/10.3390/livers3010010 - 08 Mar 2023
Cited by 1 | Viewed by 1800
Abstract
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 [...] Read more.
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. Full article
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12 pages, 3614 KiB  
Article
Single Center Experience of Oral Vancomycin Therapy in Young Patients with Primary Sclerosing Cholangitis: A Case Series
by Amala J. Alenchery, Sophia Patel, Lori Mahajan, Jacob A. Kurowski, Sarah Worley, Vera Hupertz, Kaddakal Radhakrishnan and Mohammad Nasser Kabbany
Livers 2023, 3(1), 93-104; https://doi.org/10.3390/livers3010009 - 06 Mar 2023
Viewed by 2693
Abstract
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 [...] Read more.
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. Full article
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11 pages, 560 KiB  
Review
Role of Genetic and Epigenetic Modifications in the Progression of Hepatocellular Carcinoma in Chronic HCV Patients
by Anum Syyam, Hira Raheem Akbar, Zuzana Macek Jilkova and Samia Afzal
Livers 2023, 3(1), 82-92; https://doi.org/10.3390/livers3010008 - 20 Feb 2023
Cited by 1 | Viewed by 1605
Abstract
Globally, hepatocellular carcinoma (HCC) is a significant cause of mortality and morbidity among chronically infected HCV patients. It is established that HCV is a primary risk factor for HCC progression. The treatment of HCV infection has been transformed by the introduction of DAAs [...] Read more.
Globally, hepatocellular carcinoma (HCC) is a significant cause of mortality and morbidity among chronically infected HCV patients. It is established that HCV is a primary risk factor for HCC progression. The treatment of HCV infection has been transformed by the introduction of DAAs with high rates of virological clearance. The reduction in cirrhosis-related consequences, particularly HCC, is the long-term objective of DAAs therapy for HCV. Although the risk of developing HCC is decreased in HCV patients who achieve a disease-sustaining virological response, these patients are nevertheless at risk, especially those with severe fibrosis and cirrhosis. Previous studies have shown that HCV induce several mechanisms of hepatocarcinogenesis in the host’s hepatic micro- and macro-environment, which leads to HCC progression. In an HCV-altered environment, compensatory liver regeneration favors chromosomal instability and irreversible alterations, which encourage hepatocyte neoplastic transformation and the development of malignant clones. These mechanisms involve a series of genetic and epigenetic modifications including host genetic factors, dysregulation of several signaling pathways, histone, and DNA modifications including methylation and acetylation. This review highlights the genetic and epigenetic factors that lead to the development of HCC in chronic HCV-infected individuals and can be targeted for earlier HCC diagnosis and prevention. Full article
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6 pages, 404 KiB  
Opinion
Liver Transplantation and dd-cfDNA: A Small Solution for a Big Problem
by Eleni Avramidou, Stella Vasileiadou, Nikolaos Antoniadis, Georgios Katsanos, Athanasios Kofinas, Konstantina-Eleni Karakasi and Georgios Tsoulfas
Livers 2023, 3(1), 76-81; https://doi.org/10.3390/livers3010007 - 20 Feb 2023
Viewed by 1434
Abstract
Dd-cfDNA is a novel biomarker with many diagnostic applications in various areas of medicine. In this review of the literature, we investigate its role in the diagnosis of many complications that occur in liver transplantations. In our review, we retrieved data from the [...] Read more.
Dd-cfDNA is a novel biomarker with many diagnostic applications in various areas of medicine. In this review of the literature, we investigate its role in the diagnosis of many complications that occur in liver transplantations. In our review, we retrieved data from the medical databases PubMed and Scopus. In our bibliography, many areas concerning the contributions of dd-cfDNA to the field of liver transplantation, such as in the diagnosis of complications that include signsof rejection or graft injury, are mentioned. Dd-cfDNA, which are correlated with other biomarkers such as liver enzymes, can have a high diagnostic value. Measurements of Dd-cfDNA also depend on the graft’s size and origin; therefore, these data should be taken into account for the estimation and explanation of dd-cfDNA values. Despite the utility of this novel diagnostic technique, it comes with some limitations and applicational exclusions, such as cases where there is a blood relation between the donor and recipient. Full article
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11 pages, 700 KiB  
Review
Bio-Artificial Liver Support System: A Prospective Future Therapy
by Chyntia Olivia Maurine Jasirwan, Akhmadu Muradi and Radiana Dhewayani Antarianto
Livers 2023, 3(1), 65-75; https://doi.org/10.3390/livers3010006 - 09 Feb 2023
Cited by 3 | Viewed by 5706
Abstract
Whether acute or chronic, liver failure is a state of liver dysfunction that can progress to multiorgan failure. Mortality in liver failure patients is approximately 80–90% and is caused by detoxification failure, which triggers other immediate complications, such as encephalopathy, coagulopathy, jaundice, cholestasis, [...] Read more.
Whether acute or chronic, liver failure is a state of liver dysfunction that can progress to multiorgan failure. Mortality in liver failure patients is approximately 80–90% and is caused by detoxification failure, which triggers other immediate complications, such as encephalopathy, coagulopathy, jaundice, cholestasis, and acute kidney failure. The ideal treatment for liver failure is liver transplantation, but the long waiting period for the right donor match causes unavoidable deaths in most patients. Therefore, new therapies, such as tissue engineering, hepatocyte transplantation, and stem cells, are now being studied to anticipate the patient’s condition while waiting for liver transplantation. This literature review investigated the effectiveness of some bio-artificial liver support systems using review methods systematically from international publication sites, including PubMed, using keywords, such as bio-artificial liver, acute and chronic liver failure, extracorporeal liver support system (ECLS), MARS, single-pass albumin dialysis (SPAD). Artificial and bioartificial liver systems can show specific detoxification abilities and pathophysiological improvements in liver failure patients but cannot reach the ideal criteria for actual liver function. The liver support system must provide the metabolic and synthetic function as in the actual liver while reducing the pathophysiological changes in liver failure. Aspects of safety, cost efficiency, and practicality are also considered. Identifying the technology to produce high-quality hepatocytes on a big scale is essential as a medium to replace failing liver cells. An increase in detoxification capacity and therapeutic effectiveness must also focus on patient survival and the ability to perform liver transplantation. Full article
(This article belongs to the Topic Recent Advances in Hepatology)
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2 pages, 155 KiB  
Editorial
Acknowledgment to the Reviewers of Livers in 2022
by Livers Editorial Office
Livers 2023, 3(1), 63-64; https://doi.org/10.3390/livers3010005 - 19 Jan 2023
Viewed by 647
Abstract
High-quality academic publishing is built on rigorous peer review [...] Full article
9 pages, 651 KiB  
Case Report
Lights and Shadows of Paracentesis: Is an Ultrasound Guided Approach Enough to Prevent Bleeding Complications?
by Marta Patturelli, Luca Pignata, Pietro Venetucci and Maria Guarino
Livers 2023, 3(1), 54-62; https://doi.org/10.3390/livers3010004 - 16 Jan 2023
Viewed by 2147
Abstract
Paracentesis is a validated procedure for diagnosing and managing ascites. Although paracentesis is a safe procedure with a 1–2% risk of complications such as bleeding, it is necessary to inform the patient about the possible adverse events. We would like to share our [...] Read more.
Paracentesis is a validated procedure for diagnosing and managing ascites. Although paracentesis is a safe procedure with a 1–2% risk of complications such as bleeding, it is necessary to inform the patient about the possible adverse events. We would like to share our experience with two cases of bleeding after paracentesis. In our unit, two major hemorrhagic complications occurred in 162 procedures performed over the year 2020 (frequency of bleeding complications: 1.2%). We report two clinical cases of post-paracentesis abdominal wall hematomas. Despite a similar clinical presentation, the management approach was different: in the first case, embolization of the epigastric artery supplying the hematoma was performed. In the second case, conservative treatment was adopted. Our report aims to provide food for thought about a potentially challenging hemorrhagic complication, even with the risk of adverse outcomes. Full article
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21 pages, 1388 KiB  
Review
Acetaminophen-Induced Hepatotoxicity in Obesity and Nonalcoholic Fatty Liver Disease: A Critical Review
by Karima Begriche, Clémence Penhoat, Pénélope Bernabeu-Gentey, Julie Massart and Bernard Fromenty
Livers 2023, 3(1), 33-53; https://doi.org/10.3390/livers3010003 - 12 Jan 2023
Cited by 4 | Viewed by 5145
Abstract
The epidemic of obesity, type 2 diabetes and nonalcoholic liver disease (NAFLD) favors drug consumption, which augments the risk of adverse events including liver injury. For more than 30 years, a series of experimental and clinical investigations reported or suggested that the common [...] Read more.
The epidemic of obesity, type 2 diabetes and nonalcoholic liver disease (NAFLD) favors drug consumption, which augments the risk of adverse events including liver injury. For more than 30 years, a series of experimental and clinical investigations reported or suggested that the common pain reliever acetaminophen (APAP) could be more hepatotoxic in obesity and related metabolic diseases, at least after an overdose. Nonetheless, several investigations did not reproduce these data. This discrepancy might come from the extent of obesity and steatosis, accumulation of specific lipid species, mitochondrial dysfunction and diabetes-related parameters such as ketonemia and hyperglycemia. Among these factors, some of them seem pivotal for the induction of cytochrome P450 2E1 (CYP2E1), which favors the conversion of APAP to the toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI). In contrast, other factors might explain why obesity and NAFLD are not always associated with more frequent or more severe APAP-induced acute hepatotoxicity, such as increased volume of distribution in the body, higher hepatic glucuronidation and reduced CYP3A4 activity. Accordingly, the occurrence and outcome of APAP-induced liver injury in an obese individual with NAFLD would depend on a delicate balance between metabolic factors that augment the generation of NAPQI and others that can mitigate hepatotoxicity. Full article
(This article belongs to the Special Issue Recent Advances in Acetaminophen Hepatotoxicity)
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12 pages, 841 KiB  
Opinion
Metabolic Associated Fatty Liver Disease as a Risk Factor for the Development of Central Nervous System Disorders
by Sayuri Yoshikawa, Kurumi Taniguchi, Haruka Sawamura, Yuka Ikeda, Tomoko Asai, Ai Tsuji and Satoru Matsuda
Livers 2023, 3(1), 21-32; https://doi.org/10.3390/livers3010002 - 05 Jan 2023
Cited by 4 | Viewed by 2939
Abstract
MAFLD/NAFLD is the most ordinary liver disease categorized by hepatic steatosis with the increase of surplus fat in the liver and metabolic liver dysfunction, which is associated with bigger mortality and a high medical burden. An association between MAFLD/NAFLD and central nervous system [...] Read more.
MAFLD/NAFLD is the most ordinary liver disease categorized by hepatic steatosis with the increase of surplus fat in the liver and metabolic liver dysfunction, which is associated with bigger mortality and a high medical burden. An association between MAFLD/NAFLD and central nervous system disorders including psychological disorders has been demonstrated. Additionally, MAFLD/NAFLD has been correlated with various types of neurodegenerative disorders such as amyotrophic lateral sclerosis or Parkinson’s disease. Contrasted to healthy controls, patients with MAFLD/NAFLD have a greater prevalence risk of extrahepatic complications within multiple organs. Dietary interventions have emerged as effective strategies for MAFLD/NAFLD. The PI3K/AKT/mTOR signaling pathway involved in the regulation of Th17/Treg balance might promote the pathogenesis of several diseases including MAFLD/NAFLD. As extrahepatic complications may happen across various organs including CNS, cooperative care with individual experts is also necessary for managing patients with MAFLD/NAFLD. Full article
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20 pages, 706 KiB  
Review
Support Needs and Coping Strategies in Non-Alcoholic Fatty Liver Disease (NAFLD): A Multidisciplinary Approach to Potential Unmet Challenges beyond Pharmacological Treatment
by Sue Shea, Christos Lionis, Lou Atkinson, Chris Kite, Lukasz Lagojda, Surinderjeet S. Chaggar, Ioannis Kyrou and Harpal S. Randeva
Livers 2023, 3(1), 1-20; https://doi.org/10.3390/livers3010001 - 23 Dec 2022
Cited by 2 | Viewed by 2818
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most frequently occurring chronic liver disease, affecting approximately 25–30% of the adult general population worldwide. NAFLD reflects excess hepatic accumulation of fat in the absence of increased alcohol intake, and, due to its close association with [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) is the most frequently occurring chronic liver disease, affecting approximately 25–30% of the adult general population worldwide. NAFLD reflects excess hepatic accumulation of fat in the absence of increased alcohol intake, and, due to its close association with obesity, is frequently referred to as the ‘hepatic manifestation’ of metabolic syndrome. Indeed, a high percentage of individuals with NAFLD present with a combination of the cardio-metabolic comorbidities that are associated with the metabolic syndrome. In addition to its well-established link with the metabolic syndrome and increased risk for cardiovascular disease, NAFLD has also been associated with certain mental health issues (e.g., depression and stress). Although this link is now being increasingly recognized, there are still unmet needs regarding the holistic management of patients with NAFLD, which could further contribute to feelings of social isolation and loneliness. The latter conditions are also increasingly reported to pose a substantial risk to overall health and quality of life. To date, there is limited research that has explored these issues among patients with NAFLD, despite existing data which indicate that perceived loneliness and isolation may pose an additional health risk. Notably, many features associated with NAFLD have been related to these concepts, such as perceived stigma, fatigue, stress, and confusion regarding this diagnosis. As such, this review aimed to assess such potential problems faced by patients with NAFLD, and to explore the possibility of unmet support needs which could lead to perceived social isolation. Moreover, the importance of a compassionate approach towards such patients is discussed, together with potential coping strategies. Future research directions and the need for a multidisciplinary approach are also highlighted. Full article
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