Liver cirrhosis and immune dysfunction

Hasa, Elda; Hartmann, Phillipp; Schnabl, Bernd

doi:10.1093/intimm/dxac030

Cited by 20 publications

(9 citation statements)

References 179 publications

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“…Similar immune dysfunction has been noted in patients with cirrhosis who experience increased susceptibility to bacterial infection in the setting of extensive immunoparesis 46. Findings in cirrhotics of intestinal dysmotility, intestinal permeability, and gut microbiome dysbiosis that contribute to infections can also explain the increased infection risk seen in MAFLD 47…”

Section: Discussionmentioning

confidence: 76%

Association of metabolic dysfunction-associated fatty liver disease with gastrointestinal infections: insights from National Inpatient Sample Database

Patel,

Sohal,

Bains

et al. 2024

BMJ Open Gastroenterol

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ObjectivesThe study aimed to compare the risk of gastrointestinal infections among patients with and without metabolic dysfunction-associated fatty liver disease (MAFLD).MethodsThis was a population-based, retrospective, observational study using data from the National Inpatient Sample (NIS), the largest all-payer US inpatient care database.SettingHospitalisation of adults aged ≥18 years old admitted in 2020 was identified using the NIS. Patients were stratified by the presence and absence of MAFLD.Participants26.4 million adults aged ≥18 years old were included in the study. Patients younger than 18 and those with missing demographic or mortality data were excluded.Primary and secondary outcomesPrimary outcome was to assess the overall risk of gastrointestinal infections in patients with and without MAFLD. Secondary outcomes were demographics and comorbidities stratified by the presence or absence of gastrointestinal infection, and the risk of specific gastrointestinal pathogens.ResultsOf 26.4 million patients admitted in 2020, 755 910 (2.85%) had the presence of MAFLD. There was a higher prevalence of bacterial gastrointestinal infections in patients with MAFLD than those without (1.6% vs 0.9%, p<0.001). The incidence ofClostridioides difficile(1.3% vs 0.8%, p<0.001),Escherichia coli(0.3% vs 0.01%, p<0.001), andSalmonella(0.07% vs 0.03%, p<0.001) was higher in patients with MAFLD. The presence of MAFLD was associated with higher odds of developing gastrointestinal infections (adjusted OR (aOR) −1.75, 95% CI −1.68 to 1.83, p<0.001). After adjusting for confounders, results remained statistically significant (aOR −1.36, 95% CI - 1.30-1.42, p<0.001).ConclusionEven after adjusting for confounding factors, our study demonstrates an increased risk of gastrointestinal infections in patients with MAFLD, specifically ofC. difficile,E. coli, andSalmonella. The immune and microbiota changes seen within MAFLD potentially contribute to the increased risk of gastrointestinal infections.

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Section: Discussionmentioning

confidence: 76%

Association of metabolic dysfunction-associated fatty liver disease with gastrointestinal infections: insights from National Inpatient Sample Database

Patel,

Sohal,

Bains

et al. 2024

BMJ Open Gastroenterol

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“…Of note, cirrhosis was regarded as an end-stage liver disease stemming from a variety of etiologies. It is ascertained that cirrhosis accompanies with moderate to severe systemic inflammation, manifested by overproduction of inflammatory cytokines, oxidative stress and culmination of activated neutrophils/macrophages in the circulation and the hepatic tissues [30]. Furthermore, the “immune paralysis” or immune deficiency is always observed, which is coined as the cirrhosis-associated immune dysfunction in agreement with the severity of hepatic insufficiency and organ failure [31, 32].…”

Section: Methodsmentioning

confidence: 99%

Coexistent GLIM-Defined Malnutrition and Sarcopenia Increase the Long-Term Mortality Risk in Hospitalized Patients with Decompensated Cirrhosis

Wang,

et al. 2023

Ann Nutr Metab

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Introduction: The synergistic impact of coexistent malnutrition and sarcopenia on morality in hospitalized patients with decompensated cirrhosis remains elusive. This prospective cohort study aimed to delineate the prevalence concerning coexistence of malnutrition and sarcopenia and the prognosticating role on long-term mortality among cirrhosis. Methods: Adult cirrhotic patients with decompensated episodes between 2019 and 2021 were consecutively enrolled. Malnutrition and sarcopenia were diagnosed according to the Global Leadership Initiative on Malnutrition (GLIM) criteria and the European Working Group on Sarcopenia in Older People (EWGSOP2) algorithm, respectively. The entire cohort was divided into three groups: non-malnutrition and non-sarcopenia (NN), malnutrition or sarcopenia and coexistent malnutrition and sarcopenia (MS). Log-rank test and multivariate Cox regression model were utilized to evaluate survival status and independent risk factors for mortality, respectively. Results: Our findings indicated that malnutrition manifested 44.6% of inpatients with decompensated cirrhosis, while sarcopenia presented in 16.4% of the entire cohort, indicative of a prevalence of 14.7% regarding coexistent malnutrition and sarcopenia. The Kaplan-Meier graphic demonstrated a significant difference regarding survival curves among the three groups, referring to the MS group presented with the lowest survival rate (log-rank test: P <0.001). Moreover, coexistent malnutrition and sarcopenia were associated with nearly 4 times higher mortality risk (model 1: HR=3.31, 95% CI: 1.20-9.13, P=0.020; model 2: HR=4.34, 95% CI: 1.52-12.4, P=0.006) in comparison with patients without any condition (NN group). Conclusions: Malnutrition and sarcopenia had superimposed negative impacts on inpatients with decompensated cirrhosis. It is imperative to identify these vulnerable subset to provide prompt therapeutic intervention for better prognosis.

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“…Furthermore, cirrhosis and acute-on-chronic liver failure (ACLF) are associated with severe systemic inflammation, respectively, with oxidative stress, increased inflammatory cytokines, and some markers of activated macrophages and neutrophils in the liver and in the blood. 166 In liver cirrhosis, an immune deficiency or “immune paralysis” is often observed – cirrhosis-associated immune dysfunction (CAID) syndrome. 167 The intensity of CAID syndrome correlates with the severity of acute/chronic liver failure and bacterial translocation.…”

Section: Hev Among Individuals With Chronic Liver Diseasementioning

confidence: 99%

Hepatitis E Virus (HEV) Infection Among Immunocompromised Individuals: A Brief Narrative Review

Alexandrova,

Tsachev,

Kirov

et al. 2024

IDR

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Hepatitis E virus (HEV) is a single-stranded positive-sense RNA virus that belongs to Hepeviridae family. HEV is the most common cause of acute viral hepatitis worldwide. According to the World Health Organization (WHO), there are estimated 20 million HEV infections worldwide every year, leading to estimated 3.3 million symptomatic cases of HEV infection. The WHO estimates that HEV infection caused approximately 44,000 deaths in 2015, which represents 3.3% of mortality rates due to viral hepatitis. In low-income (LI) countries and lower-middle-income (LMI) countries, HEV is a waterborne infection induced by HEV genotype (gt) 1 and HEV gt 2 that cause large outbreaks and affect young individuals with a high mortality rate in pregnant women from South Asian countries and patients with liver diseases. HEV gt 3, HEV gt 4, and HEV gt 7 are responsible for sporadic infections with zoonotic transmission mainly through the consumption of raw or undercooked meat from different animals. Acute HEV infection is relatively asymptomatic or mild clinical form, in rare cases the disease can be moderate/severe clinical forms and result in fulminant hepatitis or acute liver failure (ALF). Furthermore, HEV infection is associated with extrahepatic manifestations, including renal and neurological clinical signs and symptoms. Pregnant women, infants, older people, immunocompromised individuals, patients with comorbidities, and workers who come into close contact with HEV-infected animals are recognized as major risk groups for severe clinical form of HEV infection and fatal outcome. Chronic HEV infection can occur in immunocompromised individuals with the possibility of progression to cirrhosis.

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Liver cirrhosis and immune dysfunction

Cited by 20 publications

References 179 publications

Association of metabolic dysfunction-associated fatty liver disease with gastrointestinal infections: insights from National Inpatient Sample Database

Association of metabolic dysfunction-associated fatty liver disease with gastrointestinal infections: insights from National Inpatient Sample Database

Coexistent GLIM-Defined Malnutrition and Sarcopenia Increase the Long-Term Mortality Risk in Hospitalized Patients with Decompensated Cirrhosis

Hepatitis E Virus (HEV) Infection Among Immunocompromised Individuals: A Brief Narrative Review

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