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Liver and Infection
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Liver and Infection

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Physiology and Pathology".

Deadline for manuscript submissions: closed (16 November 2022) | Viewed by 21591

Special Issue Editors

Dr. William Nseir

E-Mail Website
Guest Editor
Department of Internal Medicine A, Baruch Padeh Medical Center and Azrieli Faculty of Medicine, Safed, Bar-Ilan University, M.P. Lower Galille 15208, Poriya, Israel
Interests: chronic viral hepatitis; NAFLD; sepsis; immune response; infectious diseases
Dr. Neven Papic

E-Mail Website
Guest Editor
Department of infectious diseases, University of Zagreb School of Medicine, Zagreb, Croatia
Interests: chronic viral hepatitis; NAFLD; sepsis; immune response; infectious diseases

Special Issue Information

Dear Colleagues,

This Special Issue will focus on infections in patients with liver diseases, including pathogenesis, immunology, clinical presentation, etiology, diagnosis, and treatment. The liver, with its ability to produce acute phase proteins, complement proteins and cytokines, plays a central role in regulating inflammation. A balanced pro- and anti-inflammatory liver response results in pathogen clearance and resolution of inflammation. Liver dysfunction during sepsis in patients without pre-existing liver disease is an independent predictor of mortality. The risk of developing bacterial infections is further enhanced in patients with liver cirrhosis, making them ten times more susceptible to bloodstream infections and resulting in a fourfold increase in mortality. Furthermore, the epidemiology and etiology of bacteriemia in liver cirrhosis patients is currently changing.

While survival following liver transplantation has dramatically increased owing to an improvement in surgical techniques and immunosuppression, infectious complications are a major source of morbidity and mortality in liver transplant recipients.

While non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in Western countries, the impact of NAFLD on bacterial infections has only recently started to be explored. Patients with NAFLD have been described to have more common recurrent bacterial infections, urinary tract infections, bacteriemia of gastrointestinal origin, Clostridioides difficile enterocolitis, and more severe pneumonia. Recently, COVID-19 has highlighted the importance of NAFLD in outcomes of severe viral infections. There is growing evidence that immunological changes in patients with NAFLD might have a profound impact in the course of infectious diseases—a place where we have not been looking so far. The rapidly increasing prevalence of NAFLD requires novel therapeutic and prophylactic approaches based on better understanding of the immunopathogenesis of infections in these patients.

The aim of this interdisciplinary issue is to bring together experts from different fields in promoting this important topic.

Dr. William Nseir
Dr. Neven Papic
Guest Editors

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Keywords

  • liver diseases
  • non-alcoholic fatty liver disease
  • liver cirrhosis
  • liver transplantation
  • infections
  • sepsis
  • COVID-19

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Published Papers (7 papers)

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Research

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13 pages, 1014 KiB  
Article
The Impact of Nonalcoholic Fatty Liver Disease on Severe Community-Acquired Pneumonia Outcomes
by Branimir Gjurašin, Mia Jeličić, Marko Kutleša and Neven Papić
Life 2023, 13(1), 36; https://doi.org/10.3390/life13010036 - 23 Dec 2022
Cited by 7 | Viewed by 2463
Abstract
Community-acquired pneumonia (CAP) is one of the leading causes of morbidity and mortality, while nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. NAFLD is associated with systemic changes in immune response, possibly linked to CAP severity. However, [...] Read more.
Community-acquired pneumonia (CAP) is one of the leading causes of morbidity and mortality, while nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. NAFLD is associated with systemic changes in immune response, possibly linked to CAP severity. However, the impact of NAFLD on CAP outcomes has not been determined. The aim of this study was to evaluate clinical course, complications and outcomes of severe CAP requiring ICU treatment in patients with NAFLD in the pre-COVID-19 era. A retrospective cohort study included 138 consecutively hospitalized adult patients with severe CAP admitted to the ICU during a 4-year period: 80 patients with NAFLD and 58 controls. Patients with NAFLD more frequently presented with ARDS (68.7% vs. 43.1%), and required invasive mechanical ventilation (86.2% vs. 63.8%), respiratory ECMO (50% vs. 24.1%), and continuous renal replacement therapy (62.5% vs. 29.3%). Mortality was significantly higher in the NAFLD group (50% vs. 20.7%), and the time from hospital admission to death was significantly shorter. In survival analysis, NAFLD (HR 2.21, 95%CI 1.03–5.06) was associated with mortality independently of other components of metabolic syndrome. In conclusion, our study identified NAFLD as an independent predictor of mortality in patients with severe CAP. Full article
(This article belongs to the Special Issue Liver and Infection)
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13 pages, 1340 KiB  
Article
Distinct Cytokine Profiles in Severe COVID-19 and Non-Alcoholic Fatty Liver Disease
by Neven Papic, Lara Samadan, Nina Vrsaljko, Leona Radmanic, Karlo Jelicic, Petra Simicic, Petra Svoboda, Snjezana Zidovec Lepej and Adriana Vince
Life 2022, 12(6), 795; https://doi.org/10.3390/life12060795 - 26 May 2022
Cited by 10 | Viewed by 2672
Abstract
Non-alcoholic fatty liver disease (NAFLD) is identified as a risk factor for developing severe COVID-19. While NAFLD is associated with chronic low-grade inflammation, mechanisms leading to immune system hyperactivation remain unclear. The aim of this prospective observational study is to analyze cytokine profiles [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) is identified as a risk factor for developing severe COVID-19. While NAFLD is associated with chronic low-grade inflammation, mechanisms leading to immune system hyperactivation remain unclear. The aim of this prospective observational study is to analyze cytokine profiles in patients with severe COVID-19 and NAFLD. A total of 94 patients with severe COVID-19 were included. Upon admission, clinical and laboratory data were collected, a liver ultrasound was performed to determine the presence of steatosis, and subsequently, 51 were diagnosed with NAFLD according to the current guidelines. There were no differences in age, sex, comorbidities, and baseline disease severity between the groups. Serum cytokine concentrations were analyzed using a multiplex bead-based assay by flow cytometry. Upon admission, the NAFLD group had higher C-reactive protein, procalcitonin, alanine aminotransferase, lactate dehydrogenase, and fibrinogen. Interleukins-6, -8, and -10 and CXCL10 were significantly higher, while IFN-γ was lower in NAFLD patients. Patients with NAFLD who progressed to critical illness had higher concentrations of IL-6, -8, -10, and IFN-β, and IL-8 and IL-10 appear to be effective prognostic biomarkers associated with time to recovery. In conclusion, NAFLD is associated with distinct cytokine profiles in COVID-19, possibly associated with disease severity and adverse outcomes. Full article
(This article belongs to the Special Issue Liver and Infection)
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18 pages, 4372 KiB  
Article
Anti-Inflammatory Effects of Melatonin in Rats with Induced Type 2 Diabetes Mellitus
by Hande Yapislar, Ebru Haciosmanoglu, Turkan Sarioglu, Sevgin Degirmencioglu, Ibrahim Sogut, Michael Poteser and Cem Ekmekcioglu
Life 2022, 12(4), 574; https://doi.org/10.3390/life12040574 - 12 Apr 2022
Cited by 15 | Viewed by 2842
Abstract
Introduction: Insulin resistance is associated with a pro-inflammatory state increasing the risk for complications in patients with type 2 diabetes mellitus (T2DM). In addition to its chronobiotic effects, the pineal hormone melatonin is known to exert anti-inflammatory and antioxidant effects. Melatonin was also [...] Read more.
Introduction: Insulin resistance is associated with a pro-inflammatory state increasing the risk for complications in patients with type 2 diabetes mellitus (T2DM). In addition to its chronobiotic effects, the pineal hormone melatonin is known to exert anti-inflammatory and antioxidant effects. Melatonin was also suggested to affect insulin secretion. The aim of this study was therefore to investigate the effect of melatonin on inflammation in diabetic rats and to study the possible involvement of the melatonin receptor, MT2. Materials and Methods: Male Sprague Dawley rats were randomly divided into four experimental groups (n = 10 per group): (1) control, (2) streptozotocin/nicotinamide induced diabetes type 2 (T2DM), (3) T2DM treated with melatonin (500 µg/kg/day), and (4) T2DM treated with melatonin (500 µg/kg/day for 6 weeks) and the selective MT2 receptor antagonist luzindole (0.25 g/kg/day for 6 weeks). Blood samples were taken for biochemical parameters and various tissue samples (liver, adipose tissue, brain) were removed for immunohistochemistry (IHC), Western blot (WB), and Q-PCR analyses, respectively. Results: Melatonin significantly reduced increased blood levels of liver transaminases (AST, ALT), blood urea nitrogen (BUN), triglyceride, very low-density lipoprotein (VLDL), and cholesterol in diabetic rats with luzindole treatment partly reversing this effect regarding the lipids. Furthermore, the liver and adipose tissues of T2DM rats treated with melatonin showed lower expression of the inflammatory markers IL-1β, IL-6, TNF-α, and NF-κB as compared to the T2DM group without melatonin. The results also showed that the MT2 receptor is at least partly involved in the protective effects of melatonin. Conclusions: Our results suggest that melatonin exerts relevant anti-inflammatory effects on various tissues in type 2 diabetic rats. Full article
(This article belongs to the Special Issue Liver and Infection)
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8 pages, 590 KiB  
Article
The Possible Association of Non-Alcoholic Fatty Liver Disease with Acute Cholangitis: A Retrospective Multicenter Cohort Study
by Wisam Sbeit, Moeen Sbeit, Itay Kalisky, Lior Katz, Amir Mari and Tawfik Khoury
Life 2022, 12(1), 35; https://doi.org/10.3390/life12010035 - 27 Dec 2021
Cited by 3 | Viewed by 2411
Abstract
Non-alcoholic fatty liver disease (NAFLD) is increasingly encountered. It is associated with several comorbid diseases. However, its association with infectious biliary diseases is still unknown. Aims: We aimed to assess whether NAFLD is a risk factor for the development of acute cholangitis among [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) is increasingly encountered. It is associated with several comorbid diseases. However, its association with infectious biliary diseases is still unknown. Aims: We aimed to assess whether NAFLD is a risk factor for the development of acute cholangitis among patients with common bile duct (CBD) stones. Methods: We performed a retrospective study, including all patients with a documented diagnosis of CBD stone that had available data on the presence or absence of NAFLD. Descriptive analysis using univariate and multivariate models was used to assess whether an association existed between NAFLD and acute cholangitis. Results: We included 811 patients. Of them, 161 patients presented with acute cholangitis, vs. 650 patients who presented with symptomatic CBD stone without cholangitis. NAFLD was significantly more common in the cholangitis group compared to the non-cholangitis group (15.5% vs. 8.3%, p = 0.01). In univariate analysis, age (Odds ratio (OR) 1.04, p < 0.0001), male gender (OR 1.47, p = 0.03), hypertension (OR 1.81, p = 0.0008), hyperlipidemia (OR 1.59, p = 0.01), and NAFLD (OR 2.04, p = 0.006) were significantly associated with acute cholangitis. In multivariate analysis, NAFLD kept its association with acute cholangitis irrespective of age (OR 2.15, p = 0.005). Conclusions: NALFD showed a significant association with acute cholangitis among patients with a CBD stone. Clinicians should encourage treatment of NAFLD in general, and especially in the setting of gallstone disease. Full article
(This article belongs to the Special Issue Liver and Infection)
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Review

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16 pages, 2871 KiB  
Review
Seroprevalence Trends and Molecular Epidemiology of Viral Hepatitis in Croatia
by Tatjana Vilibic-Cavlek, Snjezana Zidovec-Lepej, Thomas Ferenc, Vladimir Savic, Tatjana Nemeth-Blazic, Mateja Vujica Ferenc, Maja Bogdanic, Maja Vilibic, Bojana Simunov, Natasa Janev-Holcer, Pavle Jelicic, Dominik Ljubas, Tian Kosar, Maja Ilic, Jasmina Kucinar, Ljubo Barbic, Vladimir Stevanovic and Anna Mrzljak
Life 2023, 13(1), 224; https://doi.org/10.3390/life13010224 - 13 Jan 2023
Cited by 2 | Viewed by 2678
Abstract
Viral hepatitis is a significant cause of morbidity and mortality worldwide. In Croatia, hepatitis B virus (HBV) and hepatitis C virus (HCV) are widely distributed, especially in some high-risk groups such as people who inject drugs (PWID), prisoners, and highly promiscuous groups. The [...] Read more.
Viral hepatitis is a significant cause of morbidity and mortality worldwide. In Croatia, hepatitis B virus (HBV) and hepatitis C virus (HCV) are widely distributed, especially in some high-risk groups such as people who inject drugs (PWID), prisoners, and highly promiscuous groups. The seroprevalence of HBV ranges from 7.0% in the general population to 38.8% in PWID, depending on the region. The seroprevalence of HCV is highest among PWID (29–75.5%) as compared to 0.9% in the general population. Analyzing the distribution of HCV genotypes, no substantial changes in the molecular epidemiology of the two most frequent HCV genotypes (1 and 3) in the past 20 years were observed. However, the predominance of subtype 1b compared to subtype 1a as detected in 1996–2005 was not confirmed in 2008–2015. Hepatitis A virus (HAV) incidence was high in the past with a decreasing trend since the 2000s, except for an outbreak in 2017–2018 as part of the large European outbreak, which was mainly among men who have sex with men. Hepatitis E virus (HEV) is an emerging virus detected for the first time in Croatia in 2012. The seroprevalence of HEV is high among hemodialysis patients (27.9%) and liver transplant recipients (19.3–24.4%). In addition, higher seroprevalence rates were observed in animal-related professions (e.g., veterinarians, 15.2%; hunters, 14.9%). All detected HEV strains belonged to genotype 3. Full article
(This article belongs to the Special Issue Liver and Infection)
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16 pages, 1650 KiB  
Review
The Role of Stem Cell Factor, Epidermal Growth Factor and Angiopoietin-2 in HBV, HCV, HCC and NAFLD
by Leona Radmanić and Snježana Zidovec-Lepej
Life 2022, 12(12), 2072; https://doi.org/10.3390/life12122072 - 9 Dec 2022
Cited by 5 | Viewed by 2112
Abstract
Growth factors play a significant role in the immunopathogenesis of liver diseases, especially in liver fibrosis and cirrhosis. They can also play a role in liver regeneration and tissue repair. The regenerative capacity of the liver has been well established. Molecular mechanisms leading [...] Read more.
Growth factors play a significant role in the immunopathogenesis of liver diseases, especially in liver fibrosis and cirrhosis. They can also play a role in liver regeneration and tissue repair. The regenerative capacity of the liver has been well established. Molecular mechanisms leading to regeneration involve a complex network of diverse molecules. Chronic liver injury leads to the dysregulation of regenerative mechanisms in the liver that, in addition to molecular oncogenesis, lead to uncontrolled cell proliferation and development of hepatocellular carcinoma (HCC). Stem cell factor (SCF), epidermal growth factor (EGF) and Angiopietin-2 (Ang-2) have been shown to be extremely important in the pathogenesis of liver diseases, and given their role in hepatitis B (HBV) or C virus (HCV), HCC and nonalcoholic fatty liver disease (NAFLD), they seem to be potential targets for future research into antifibrotic drugs. The role of SCF receptor c-kit in the liver is debatable, as it has impact on both liver regeneration and liver disease. EGF is a potential indicator of the survival of patients with HCC and can be a biomarker and therapeutic target structure in HCC. Further research is needed to investigate the potential role of Ang-2 for NAFLD associated with liver damage as a non-invasive circulating biomarker. Full article
(This article belongs to the Special Issue Liver and Infection)
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17 pages, 625 KiB  
Review
The Role of Non-Alcoholic Fatty Liver Disease in Infections
by Juraj Krznarić and Adriana Vince
Life 2022, 12(12), 2052; https://doi.org/10.3390/life12122052 - 7 Dec 2022
Cited by 8 | Viewed by 5464
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease, affecting one third of the Western population. The hallmark of the disease is excessive storage of fat in the liver. Most commonly, it is caused by metabolic syndrome (or one of [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease, affecting one third of the Western population. The hallmark of the disease is excessive storage of fat in the liver. Most commonly, it is caused by metabolic syndrome (or one of its components). Even though the development of NAFLD has multiple effects on the human organism resulting in systemic chronic low-grade inflammation, this review is focused on NAFLD as a risk factor for the onset, progression, and outcomes of infectious diseases. The correlation between NAFLD and infections is still unclear. Multiple factors (obesity, chronic inflammation, altered immune system function, insulin resistance, altered intestinal microbiota, etc.) have been proposed to play a role in the development and progression of infections in people with NAFLD, although the exact mechanism and the interplay of mentioned factors is still mostly hypothesized. In this article we review only the selection of well-researched topics on NAFLD and infectious diseases (bacterial pneumonia, COVID, H. pylori, urinary tract infections, C. difficile, bacteremia, hepatitis B, hepatitis C, HIV, and periodontitis). Full article
(This article belongs to the Special Issue Liver and Infection)
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