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Livers, Volume 4, Issue 2 (June 2024) – 8 articles

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7 pages, 768 KiB  
Brief Report
Infection-Related Readmissions Are Rising among Patients with Hepatorenal Syndrome: A Nationwide Analysis
by Umer Farooq, Zahid I. Tarar, Ammad J. Chaudhary, Abdallah E. Alayli, Faisal Kamal, Chengdu Niu and Kamran Qureshi
Livers 2024, 4(2), 268-274; https://doi.org/10.3390/livers4020019 (registering DOI) - 30 May 2024
Abstract
Hepatorenal syndrome (HRS) is a unique form of renal dysfunction that results from circulatory hemodynamic dysfunction in advanced liver disease. We aimed to determine longitudinal trends in both all-cause and cause-specific readmissions for HRS in the United States. Using the National Readmission Database [...] Read more.
Hepatorenal syndrome (HRS) is a unique form of renal dysfunction that results from circulatory hemodynamic dysfunction in advanced liver disease. We aimed to determine longitudinal trends in both all-cause and cause-specific readmissions for HRS in the United States. Using the National Readmission Database (2010–2018), we identified adult HRS patients during index admission via ICD codes. Fisher’s exact test and Cox regression analysis were used to compare proportions and compute adjusted p-values, respectively. Regression models were adjusted for gender, age, the Charlson comorbidity index, median household income, and hospital factors. A total of 169,522 HRS patients were included in the analysis (overall mean age 58.97 years). The incidence of HRS hospitalization increased from 5.30% in 2010 to 5.84% in 2018 (p < 0.01). Over the same duration, all-cause readmission at 30 days showed an overall increasing trend from 19.81% to 19.99% (trend p < 0.01). HRS-specific readmission at 30 days following an index hospitalization ranged from 13.60 to 15.98, with an overall increasing trend in the study period (2010–2018). While cirrhosis, hepatic failure, and infection were uniformly the three most common causes of readmission throughout the study period, cirrhosis and infection showed an upward trend. Rising readmissions, especially with hepatic failure and infection, in HRS patients signal a need for national strategies to manage and prevent HRS towards reducing its healthcare burden. Full article
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15 pages, 3406 KiB  
Article
Understanding the Liver’s Role in the Clearance of Aβ40
by Glen P. Lockwood, Nicholas J. Hunt, Maaike Kockx, Sun Woo Sophie Kang, David G. Le Couteur and Victoria C. Cogger
Livers 2024, 4(2), 253-267; https://doi.org/10.3390/livers4020018 - 23 May 2024
Viewed by 243
Abstract
The clearance of peripheral beta amyloid (Aβ) is a potential target for the treatment of Alzheimer’s disease (AD). The liver has been implicated in the elimination of Aβ from the peripheral circulation. Here, the single-pass uptake of Aβ40 in perfused livers from young [...] Read more.
The clearance of peripheral beta amyloid (Aβ) is a potential target for the treatment of Alzheimer’s disease (AD). The liver has been implicated in the elimination of Aβ from the peripheral circulation. Here, the single-pass uptake of Aβ40 in perfused livers from young and old rats (6 to 10 rats per group) was investigated with the multiple indicator dilution technique. Aβ40 had volumes of distribution between those of the vascular marker Evans Blue and the extracellular marker sucrose. The hepatic extraction of Aβ40 was negligible, explained in part by the small permeability surface area products consistent with a high endothelial barrier to liver uptake. There were no substantial effects of age on any of these results. In vitro experiments with isolated hepatocytes and liver sinusoidal endothelial cells showed only very small amounts of Aβ uptake consistent with low intrinsic clearance. These results indicate that the hepatic clearance of Aβ is capacity-limited, explained by the low-permeability surface area products and hepatocyte uptake. However, this does not preclude an effect of aging in longer-term in vivo studies where age-related changes in liver blood flow and protein binding influence liver clearance. Full article
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13 pages, 1099 KiB  
Review
Autoimmune Hepatitis Management: Recent Advances and Future Prospects
by Rebeca Sierra, Ana Marenco-Flores, Marwan Alsaqa, Romelia Barba, Marcela Cuellar-Lobo, Carla Barberan and Leandro Sierra
Livers 2024, 4(2), 240-252; https://doi.org/10.3390/livers4020017 - 15 May 2024
Viewed by 417
Abstract
Autoimmune hepatitis (AIH) is a varied inflammatory chronic liver disease. AIH’s prevalence varies and has increased recently. Diagnosis involves the discovery of histologic features following liver biopsy and serologic testing. Clinical features vary, and up to 40% of patients may be asymptomatic. Evaluating [...] Read more.
Autoimmune hepatitis (AIH) is a varied inflammatory chronic liver disease. AIH’s prevalence varies and has increased recently. Diagnosis involves the discovery of histologic features following liver biopsy and serologic testing. Clinical features vary, and up to 40% of patients may be asymptomatic. Evaluating thiopurine methyltransferase (TMPM) activity before treatment is crucial for an optimal response. The primary treatment goal is biochemical remission, normalized serum IgG, and liver enzymes. Induction therapy typically involves azathioprine and corticosteroids. Close monitoring of liver function tests and serum immunoglobulin levels is essential. Medications can be tapered after achieving biochemical remission. Liver transplantation may be required for refractory disease or cirrhosis. Further therapeutic approaches are needed, particularly for non-responders to first-line treatments. Full article
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32 pages, 6718 KiB  
Article
Understanding the SARS-CoV-2–Human Liver Interactome Using a Comprehensive Analysis of the Individual Virus–Host Interactions
by Giovanni Colonna
Livers 2024, 4(2), 209-239; https://doi.org/10.3390/livers4020016 - 30 Apr 2024
Viewed by 355
Abstract
Many metabolic processes at the molecular level support both viral attack strategies and human defenses during COVID-19. This knowledge is of vital importance in the design of antiviral drugs. In this study, we extracted 18 articles (2021–2023) from PubMed reporting the discovery of [...] Read more.
Many metabolic processes at the molecular level support both viral attack strategies and human defenses during COVID-19. This knowledge is of vital importance in the design of antiviral drugs. In this study, we extracted 18 articles (2021–2023) from PubMed reporting the discovery of hub nodes specific for the liver during COVID-19, identifying 142 hub nodes. They are highly connected proteins from which to obtain deep functional information on viral strategies when used as functional seeds. Therefore, we evaluated the functional and structural significance of each of them to endorse their reliable use as seeds. After filtering, the remaining 111 hubs were used to obtain by STRING an enriched interactome of 1111 nodes (13,494 interactions). It shows the viral strategy in the liver is to attack the entire cytoplasmic translational system, including ribosomes, to take control of protein biosynthesis. We used the SARS2-Human Proteome Interaction Database (33,791 interactions), designed by us with BioGRID data to implement a reverse engineering process that identified human proteins actively interacting with viral proteins. The results show 57% of human liver proteins are directly involved in COVID-19, a strong impairment of the ribosome and spliceosome, an antiviral defense mechanism against cellular stress of the p53 system, and, surprisingly, a viral capacity for multiple protein attacks against single human proteins that reveal underlying evolutionary–topological molecular mechanisms. Viral behavior over time suggests different molecular strategies for different organs. Full article
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16 pages, 1934 KiB  
Article
The Effect of Barley Bran Polyphenol-Rich Extracts on the Development of Nonalcoholic Steatohepatitis in Sprague–Dawley Rats Fed a High-Fat and High-Cholesterol Diet
by Katsuhisa Omagari, Juna Ishida, Konomi Murata, Ryoko Araki, Mizuki Yogo, Bungo Shirouchi, Kazuhito Suruga, Nobuko Sera, Kazunori Koba, Mayuko Ichimura-Shimizu and Koichi Tsuneyama
Livers 2024, 4(2), 193-208; https://doi.org/10.3390/livers4020015 - 24 Apr 2024
Viewed by 528
Abstract
Oxidative stress and inflammation play a central role in the progression of nonalcoholic steatohepatitis (NASH), which can lead to liver cirrhosis. Barley bran has potential bioactivities due to its high content of functional substances, such as anthocyanins, with anti-inflammatory and anti-oxidative properties. Here, [...] Read more.
Oxidative stress and inflammation play a central role in the progression of nonalcoholic steatohepatitis (NASH), which can lead to liver cirrhosis. Barley bran has potential bioactivities due to its high content of functional substances, such as anthocyanins, with anti-inflammatory and anti-oxidative properties. Here, we investigated whether barley bran polyphenol-rich extracts (BP) can prevent NASH in Sprague–Dawley rats fed a high-fat and high-cholesterol diet including 1.25% or 2.5% cholesterol for 9 weeks. In the rat model of NASH with advanced hepatic fibrosis, BP prevented NASH development by ameliorating the histopathological findings of lobular inflammation. The BP also tended to attenuate serum aspartate aminotransferase level in this model. In the rat model of NASH with mild-to-moderate hepatic fibrosis, BP tended to attenuate the serum levels of transaminases. BP-dose-dependent effects were revealed for several parameters, including monocyte chemoattractant protein-1, transforming growth factor-β, and manganese superoxide dismutase gene expressions in the liver. These results suggest that BP may prevent NASH development or progression, presumably due to its anti-inflammatory and anti-oxidative properties. Full article
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11 pages, 931 KiB  
Article
Validation and Comparison of Non-Invasive Tests for the Exclusion of High-Risk Varices in Compensated Advanced Chronic Liver Disease
by Rajiv Kurup, Eric Kalo, Scott Read, Wai See Ma, Jacob George and Golo Ahlenstiel
Livers 2024, 4(2), 182-192; https://doi.org/10.3390/livers4020014 - 12 Apr 2024
Viewed by 669
Abstract
Non-invasive tests (NITs) are a potential alternative to screening oesophagogastroduodenoscopy (OGD) for ruling out high-risk varices (HRVs) in patients with compensated advanced chronic liver disease (cACLD). This retrospective study aimed to externally validate and compare various NITs in a multi-centre Australian cohort. Patients [...] Read more.
Non-invasive tests (NITs) are a potential alternative to screening oesophagogastroduodenoscopy (OGD) for ruling out high-risk varices (HRVs) in patients with compensated advanced chronic liver disease (cACLD). This retrospective study aimed to externally validate and compare various NITs in a multi-centre Australian cohort. Patients with cACLD were enrolled between January 2013 and December 2022. Liver stiffness measurements (LSMs), clinicopathological data, and OGD results were collected. A total of 210 patients were included. The median age was 57 years and 65.7% were male. The main aetiology of cACLD was hepatitis C (41.9%), and 91.9% of patients were Child–Pugh A. HRV prevalence was 12.4%. The Baveno VI criteria (B6C) was the only NIT that could safely reduce the need for OGDs across all aetiologies of cACLD, with a negative predictive value of 98.6 and spared OGD in 33.8%. The FIB-4 would have avoided the most OGDs (71%); however, the HRV miss rate was 6%. The results suggest that the B6C is the best performing NIT in our cohort and reliably excludes HRVs in cACLD patients, regardless of aetiology. This study confirms that the Baveno VI criteria can be applied in an Australian, mixed aetiology cohort to avoid unnecessary screening OGD. Full article
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10 pages, 238 KiB  
Review
The Epidemiology of Chronic Hepatitis C: Where We Are Now
by Cristina Stasi, Caterina Milli, Fabio Voller and Caterina Silvestri
Livers 2024, 4(2), 172-181; https://doi.org/10.3390/livers4020013 - 30 Mar 2024
Cited by 1 | Viewed by 958
Abstract
One of the main objectives of the World Health Organization is the eradication of viral hepatitis by 2030 by identifying subjects before disease progression. In 2019, only 21% of the 58 million people chronically infected with hepatitis C virus (HCV) had been diagnosed, [...] Read more.
One of the main objectives of the World Health Organization is the eradication of viral hepatitis by 2030 by identifying subjects before disease progression. In 2019, only 21% of the 58 million people chronically infected with hepatitis C virus (HCV) had been diagnosed, while overall 13% had been treated. The key recommendation of international screening programs is to reach the people at major risk of viral hepatitis and the general population. National plans, including that in Italy, have dedicated budget lines to support efforts to achieve the objective of elimination. The Italian program involves free screening for HCV in the general population born between 1969 and 1989 and also for all persons in the care of addiction services (Ser.D) and prisoners. The screening programs differed slightly among regions in Italy. In particular, referring to the screening for people born in the period of 1969–1989, in Tuscany, these people received an invitation by SMS to undergo a HCV antibody test. If the test results were positive, the subject was registered on a regional platform and required to undergo HCV RNA testing, prescribed by their GP. In the case of testing positive for HCV RNA, the linkage to care (i.e., patient entry into specialist care after diagnosis) is guaranteed. A strong effort is currently required to eliminate HCV effectively. This review highlights the most recent changes to the epidemiological scenario at the global, European, Italian, and regional (Tuscany) levels. Full article
(This article belongs to the Special Issue Viral Hepatitis: Prevention, Infection, and Treatment)
8 pages, 526 KiB  
Case Report
Serendipity in Medicine-Elevated Immunoglobulin E Levels Associated with Excess Alcohol Consumption
by Stephen D. H. Malnick, Ali Abdullah, Fadi Ghanem, Sheral Ohayon Michael and Manuela G. Neuman
Livers 2024, 4(2), 164-171; https://doi.org/10.3390/livers4020012 - 25 Mar 2024
Viewed by 594
Abstract
Making a diagnosis of alcoholic liver disease is not always easy. There are problems in obtaining an accurate and reliable history of alcohol consumption. Laboratory findings and hepatic imaging studies are neither sensitive or specific, and newer test are being considered. Recently, a [...] Read more.
Making a diagnosis of alcoholic liver disease is not always easy. There are problems in obtaining an accurate and reliable history of alcohol consumption. Laboratory findings and hepatic imaging studies are neither sensitive or specific, and newer test are being considered. Recently, a patient was admitted with possible alcoholic hepatitis. The first-year resident who admitted the patient mistakenly ordered a blood test for serum IgE. The result was a markedly elevated −6440 IU/mL. There was no evidence of parasitic infections, atopy or autoimmune disease nor was there any eosinophilia. A literature search showed that elevated IgE levels are associated with alcohol abuse. This association has been forgotten and does not appear in standard reference sources such as UptoDate or Harrison’s Principles of Internal Medicine. This judicious use of examining serum IgE levels may aid in the diagnosis of alcoholic hepatitis. Full article
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