Copeptin in acute decompensation of liver cirrhosis: relationship with acute-on-chronic liver failure and short-term survival

IntroductionAcute-on-chronic liver failure (ACLF) is characterized by high levels of systemic inflammation and parallel suppression of innate immunity, whereas little is known about adaptive immune immunity in ACLF. We therefore aimed to characterize the development of the adaptive immune system during the progression of liver cirrhosis to ACLF. Patients with compensated/stable decompensated liver cirrhosis, acute decompensation of liver cirrhosis, or ACLF were recruited from a prospective cohort study. Comprehensive immunophenotyping was performed using high dimensional flow cytometry. Replication of Torque teno (TT) virus was quantified as a marker of immunosuppression. High frequencies of detectable TT virus were observed already in patients with compensated/stable decompensated liver cirrhosis compared to healthy controls (>50% vs. 19%), suggesting relatively early occurrence of immunosuppression in cirrhosis. In line, profoundly reduced numbers of distinct innate and adaptive immune cell populations were observed before ACLF development. These changes were accompanied by parallel upregulation of co-stimulatory (e.g. CD40L, OX40, CD69, GITR, TIM-1) and inhibitory immune checkpoints (e.g. PDPN, PROCR, 2B4, TIGIT) on CD4+ and CD8+ T cells, which again preceded the development of ACLF. On a functional basis, the capacity of CD4+ and CD8+ T cells to produce pro-inflammatory cytokines upon stimulation was strongly diminished in patients with acute decompensation of liver cirrhosis and ACLF.ConclusionImpaired innate and—in particular—adaptive cellular immunity occurs relatively early in the pathogenesis of liver cirrhosis and precedes ACLF. This may contribute to the development of ACLF by increasing the risk of infections in patients with liver cirrhosis.

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Fecal Microbiota Transplantation in Alcohol-Associated Acute on Chronic Liver Failure: An Open-label Clinical Trial

10.21203/rs.3.rs-408638/v1 ◽

2021 ◽

Author(s):

Anima Sharma ◽

Akash Roy ◽

Madhumita Premkumar ◽

Ajay Duseja ◽

Sunil Taneja ◽

...

Keyword(s):

Liver Failure ◽

Fecal Microbiota Transplantation ◽

Fecal Microbiota ◽

Chronic Liver ◽

Clinical Severity ◽

Chronic Liver Failure ◽

Short Term ◽

Open Label ◽

Term Survival ◽

Severity Scores

Abstract Background: Severe alcoholic hepatitis (SAH) presenting as acute-on-chronic liver failure (ACLF) carries a high short-term mortality. Alteration of gut microbiota is a crucial component implicated in its pathogenesis, whose modulation has been suggested as a potential therapeutic tool. We evaluated the safety of fecal microbiota transplantation (FMT) and its efficacy in improving short-term survival and clinical severity scores in patients with SAH-ACLF.Methods: Thirty-three patients [13 in the FMT arm;20 in the standard of care arm (SOC] with SAH-ACLF were included in this open-label study. A single FMT session was administered as a freshly prepared stool suspension from pre-identified healthy family member stool donors through a nasojejunal tube. Patients were followed up on days seven, twenty-eight, and ninety. Results: Survival at twenty-eight and ninety days was significantly better in the FMT arm (100% versus 60%, P=0.01; 53.84% versus 25%, P=0.02). Hepatic encephalopathy resolved in 100% versus 57.14% (FMT versus SOC, P=0.11) patients, while ascites resolved in 100% versus 40% survivors (P=0.04). Major adverse event rates, including spontaneous bacterial peritonitis and gastrointestinal bleeding, were similar in both groups (P=0.77; P=0.70). Median IL1beta decreased by21.39% (IQR -73.67-7.63) in the FMT group, whereas it increased in the SOC by 27.44% (IQR -0.88-128.11) (P=0.01). Percentage changes in bilirubin and ALT between baseline and day seven emerged as predictors of ninety-day mortality.Conclusion: FMT is safe, improves short-term and medium-term survival, and leads to improvement in clinical severity scores in patients with SAH-ACLF.

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TLR-10 Single Nucleotide Polymorphism is Associated to Poor Short Term Survival in Cirrhotic Patients with Acute on Chronic Liver Failure Precipitated by Bacterial Infections

Journal of Hepatology ◽

10.1016/s0168-8278(16)00335-4 ◽

2016 ◽

Vol 64 (2) ◽

pp. S279-S280

Author(s):

P. Caraceni ◽

M. Domenicali ◽

M. Baldassarre ◽

F.A. Giannone ◽

E. Marasco ◽

...

Keyword(s):

Single Nucleotide Polymorphism ◽

Liver Failure ◽

Bacterial Infections ◽

Nucleotide Polymorphism ◽

Chronic Liver Failure ◽

Short Term ◽

Term Survival ◽

Single Nucleotide ◽

Cirrhotic Patients ◽

Short Term Survival

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993 Predictors of Infection-Related Acute-on-Chronic Liver Failure and Its Short-Term Mortality in Liver Cirrhosis: a Population Based Cohort Study

Gastroenterology ◽

10.1016/s0016-5085(14)63389-8 ◽

2014 ◽

Vol 146 (5) ◽

pp. S-932

Author(s):

Konstantina Sargenti ◽

Hanne Prytz ◽

Sara Bertilsson ◽

Emma Nilsson ◽

Emma Berg ◽

...

Keyword(s):

Liver Cirrhosis ◽

Cohort Study ◽

Liver Failure ◽

Population Based ◽

Chronic Liver ◽

Chronic Liver Failure ◽

Short Term ◽

Short Term Mortality

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Histologic Changes in Core-Needle Liver Biopsies From Patients With Acute-on-Chronic Liver Failure and Independent Histologic Predictors of 28-Day Mortality

Archives of Pathology & Laboratory Medicine ◽

10.5858/arpa.2021-0103-oa ◽

2021 ◽

Author(s):

Vandana Baloda ◽

Abhinav Anand ◽

Rajni Yadav ◽

Lalita Mehra ◽

Madhu Rajeshwari ◽

...

Keyword(s):

Liver Failure ◽

Hepatic Necrosis ◽

Chronic Liver ◽

Chronic Liver Failure ◽

Short Term ◽

Core Needle ◽

Short Term Mortality ◽

Acute Decompensation ◽

Liver Biopsies ◽

Lobular Inflammation

Context.— The histologic features in patients with acute-on-chronic liver failure (ACLF) are evolving and histologic indicators of patients' poor prognosis are not yet fully established. Objective.— To evaluate the independent histologic predictors of 28-day mortality in ACLF patients on core-needle liver biopsies. Design.— Core-needle biopsies from patients with a diagnosis of ACLF (n = 152) as per the European Association for the Study of the Liver criteria were included during 8 years. Liver biopsies from 98 patients with compensated chronic liver disease were included as disease controls for histologic comparison. Features of ongoing changes, such as hepatic necrosis, hepatic apoptosis, cholestasis, hepatocyte degeneration, bile ductular proliferation, Mallory Denk bodies, steatosis, and extent of liver fibrosis, were analyzed for predicting short-term mortality (28 days). A P value of <.05 was considered significant. Results.— In our cohort of ACLF patients, the following etiologies for acute decompensation were identified: alcohol, 47 of 152 (30.9%); sepsis, 24 of 152 (15.7%); hepatotropic viruses, 20 of 152 (13.1%); drug-induced liver injury, 11 of 152 (7.2%); autoimmune flare, 9 of 152 (5.9%); mixed etiologies, 5 of 152 (3.2%); and cryptogenic, 36 of 152 (23.6%). On histologic examination, hepatic necrosis (P < .001), dense lobular inflammation (P = .03), cholestasis (P < .001), ductular reaction (P = .001), hepatocyte degeneration (P < .001), and absence of advanced fibrosis stages (P < .001) were identified significantly more in ACLF patients than in disease controls on univariate analysis. On multivariate Cox regression analysis, the absence of advanced Ishak histologic activity index fibrosis stages (P = .02) and the presence of dense lobular inflammation (P = .04) were associated with increased 28-day mortality in ACLF patients. After adjusting the clinical causes of acute decompensation, only dense lobular inflammation was found as an independent predictor of short-term mortality (P = .04) in ACLF patients. Conclusions.— Dense lobular necroinflammatory activity is a clinically independent histologic predictor of 28-day short-term mortality in patients with ACLF.

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