Introduction: Liver cirrhosis requires a better prognostic definition due to the identification of different phases characterized by significant differences in mortality rates, primarily with the transition from compensated to non-acute (NAD) and acute decompensation (AD), followed by acute-on-chronic liver failure (ACLF), characterized by the highest mortality. This transition appears to be influenced by various factors involving in particular the progressive worsening of portal hypertension and systemic inflammation, alongside the emergence of infections and renal impairment. Aim: Our primary objective was to explore the interconnection and impact of bacterial infections on the natural progression of liver cirrhosis. In the second phase, we aimed to identify factors linked to the maintenance of liver compensation or the onset of NAD, AD, and ACLF conditions, considering infections, liver events and current therapy. Methods: This was a single-center cohort study, with the enrolment of consecutive patients affected by liver cirrhosis who were followed in our Liver Unit between January 2017 and December 2022, either as inpatients or outpatients. Results: A total of 456 patients were enrolled, with a median follow-up period of 43.31 months (IQR 24-72). Follow-up was discontinued in the event of liver transplant, mortality, or an episode of ACLF as defined by the EASL criteria. 70.6% were male, with a mean age of 64 ± 11 years. Based on recorded liver events and infectious episodes during follow-up, we categorized the cohort into four subgroups: NAD subgroup (70 patients), AD subgroup (151 patients), ACLF subgroup (81 patients) and compensated subgroup (154 patients). During the study period, 142 patients (31.1%) experienced at least one infectious episode, with 12.7% testing positive for MDROs colonization. Sepsis was the most prevalent type of bacterial infection (30.3%), followed by pneumonia (26.7%), urinary tract infections (20.4%) and spontaneous bacterial peritonitis (18.3%), while MDROs infections accounted for over 20% of cases. Urinary tract infections and MDROs were statistically more prevalent in the ACLF subgroup. We observed an association between MDROs colonization and hepatic decompensation, with an odds ratio (OR) of 0.33 (95% CI 0.14-0.72) for compensated patients, while colonized patients faced a threefold higher risk of developing AD (OR 3.20; 95% CI 1.65-6.48) and ACLF (OR 2.55; 95% CI 1.19-5.32). Another factor not significantly associated with liver compensation but strongly linked to the development of both AD (OR 5.69; 95% CI 2.92-11.84) and ACLF (OR 3.58; 95% CI 1.80-7.03) was portal vein thrombosis (PVT). In terms of current therapy, β-blockers (OR 2.14, 95% CI 1.33-3.49), direct oral anticoagulants (DOACs) (OR 3.28, 95% CI 1.76-6.23), and angiotensin-converting enzyme inhibitors/calcium channel blockers (ACE-i/CCBs) (OR 2.10, 95% CI 1.27-3.47) were strongly associated with liver compensation, while no protective role of statins and rifaximin was confirmed. Conclusion: Infections were confirmed to be a crucial complication for cirrhotic patients. To our knowledge, this is the first study to assess the impact of MDROs colonization and PVT on the development of liver decompensation, suggesting that a history of PVT and colonization with MDROs may predispose individuals to AD and ACLF. DOACs, β-blockers and ACE-i/CCBs could potentially influence the natural progression of liver cirrhosis, particularly in preventing AD and ACLF. Future prospective and randomized controlled studies may offer further insights into the pharmacological effects and the impact of infections on the progression of cirrhosis.

The impact of infections and other factors on the progression of liver decompensation, with a focus on acute decompensation and acute-on-chronic liver failure

Mantovani Anna
2024-01-01

Abstract

Introduction: Liver cirrhosis requires a better prognostic definition due to the identification of different phases characterized by significant differences in mortality rates, primarily with the transition from compensated to non-acute (NAD) and acute decompensation (AD), followed by acute-on-chronic liver failure (ACLF), characterized by the highest mortality. This transition appears to be influenced by various factors involving in particular the progressive worsening of portal hypertension and systemic inflammation, alongside the emergence of infections and renal impairment. Aim: Our primary objective was to explore the interconnection and impact of bacterial infections on the natural progression of liver cirrhosis. In the second phase, we aimed to identify factors linked to the maintenance of liver compensation or the onset of NAD, AD, and ACLF conditions, considering infections, liver events and current therapy. Methods: This was a single-center cohort study, with the enrolment of consecutive patients affected by liver cirrhosis who were followed in our Liver Unit between January 2017 and December 2022, either as inpatients or outpatients. Results: A total of 456 patients were enrolled, with a median follow-up period of 43.31 months (IQR 24-72). Follow-up was discontinued in the event of liver transplant, mortality, or an episode of ACLF as defined by the EASL criteria. 70.6% were male, with a mean age of 64 ± 11 years. Based on recorded liver events and infectious episodes during follow-up, we categorized the cohort into four subgroups: NAD subgroup (70 patients), AD subgroup (151 patients), ACLF subgroup (81 patients) and compensated subgroup (154 patients). During the study period, 142 patients (31.1%) experienced at least one infectious episode, with 12.7% testing positive for MDROs colonization. Sepsis was the most prevalent type of bacterial infection (30.3%), followed by pneumonia (26.7%), urinary tract infections (20.4%) and spontaneous bacterial peritonitis (18.3%), while MDROs infections accounted for over 20% of cases. Urinary tract infections and MDROs were statistically more prevalent in the ACLF subgroup. We observed an association between MDROs colonization and hepatic decompensation, with an odds ratio (OR) of 0.33 (95% CI 0.14-0.72) for compensated patients, while colonized patients faced a threefold higher risk of developing AD (OR 3.20; 95% CI 1.65-6.48) and ACLF (OR 2.55; 95% CI 1.19-5.32). Another factor not significantly associated with liver compensation but strongly linked to the development of both AD (OR 5.69; 95% CI 2.92-11.84) and ACLF (OR 3.58; 95% CI 1.80-7.03) was portal vein thrombosis (PVT). In terms of current therapy, β-blockers (OR 2.14, 95% CI 1.33-3.49), direct oral anticoagulants (DOACs) (OR 3.28, 95% CI 1.76-6.23), and angiotensin-converting enzyme inhibitors/calcium channel blockers (ACE-i/CCBs) (OR 2.10, 95% CI 1.27-3.47) were strongly associated with liver compensation, while no protective role of statins and rifaximin was confirmed. Conclusion: Infections were confirmed to be a crucial complication for cirrhotic patients. To our knowledge, this is the first study to assess the impact of MDROs colonization and PVT on the development of liver decompensation, suggesting that a history of PVT and colonization with MDROs may predispose individuals to AD and ACLF. DOACs, β-blockers and ACE-i/CCBs could potentially influence the natural progression of liver cirrhosis, particularly in preventing AD and ACLF. Future prospective and randomized controlled studies may offer further insights into the pharmacological effects and the impact of infections on the progression of cirrhosis.
2024
ACLF, AD, infections, Liver Decompensation
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/1134007
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