A mouse model of chronic liver disease progression and acute-on-chronic liver failure

2019 ◽  
Author(s):  
A Ghallab ◽  
M Maiju ◽  
R Hassan ◽  
A Zaza ◽  
U Hofmann ◽  
...  
Keyword(s):  
Liver Disease ◽  
Mouse Model ◽  
Liver Failure ◽  
Chronic Liver Disease ◽  
Disease Progression ◽  
Chronic Liver ◽  
Chronic Liver Failure ◽  
Liver Disease Progression

scholarly journals Imaging Software-Based Sarcopenia Assessment in Gastroenterology: Evolution and Clinical Meaning

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Giovanni Marasco ◽  
Sinan Sadalla ◽  
Giulio Vara ◽  
Rita Golfieri ◽  
Davide Festi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Liver Disease ◽  
Liver Failure ◽  
Chronic Liver Disease ◽  
Liver Diseases ◽  
Chronic Liver ◽  
Chronic Liver Failure ◽  
Cross Sectional ◽  
Cross Sectional Imaging ◽  
Sectional Imaging

Sarcopenia is gaining attention as a negative prognostic factor in different fields of medicine, including chronic liver failure. However, the assessment of sarcopenia in patients with liver diseases is often neglected due to unawareness of reliable tools and methods and thus is limited to research studies. Cross-sectional imaging is a diffuse diagnostic tool and is commonly performed in patients with chronic liver failure. The last advancements in radiology image analysis using dedicated software allow an easy and standardized method to assess skeletal muscle volume. Several measures can be obtained from cross-sectional imaging analysis to evaluate sarcopenia in patients affected by chronic liver disease. We aimed to review the recent advances in imaging-based sarcopenia assessment, in particular in patients with chronic liver diseases. As a result, we found that the skeletal muscle index (SMI) seems to be a reliable method to assess sarcopenia in cirrhotic patients. Even if further studies are needed to validate proper cut-offs for each clinical endpoint, physicians are invited to consider the assessment of sarcopenia in the work-up of patients with chronic liver disease.

scholarly journals Hepatic NF-kB-inducing Kinase (NIK) Suppresses Liver Regeneration in Chronic Liver Disease

2017 ◽  
Author(s):  
Yi Xiong ◽  
Adriana Souza Torsoni ◽  
Feihua Wu ◽  
Hong Shen ◽  
Yan Liu ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Regeneration ◽  
Chronic Liver Disease ◽  
Disease Progression ◽  
Cell Cycle Progression ◽  
Metabolic Stress ◽  
Chronic Liver ◽  
Hepatocyte Proliferation ◽  
Stat3 Pathway ◽  
Liver Disease Progression

SummaryHepatocyte replication maintains liver homeostasis and integrity. It is impaired in chronic liver disease, promoting disease progression. Herein, we have identified NF-kB-inducing kinase (NIK) as an unrecognized suppressor of hepatocyte replication. Hepatic NIK was aberrantly activated in chronic liver disease. Hepatocyte-specific deletion of NIK or its downstream mediator IKKα substantially accelerated hepatocyte proliferation and liver regeneration following partial hepatectomy. Mechanistically, NIK and IKKα suppressed the mitogenic JAK2/STAT3 pathway, thereby inhibiting hepatocyte cell cycle progression. Remarkably, inactivation of hepatic NIK largely reversed suppression of the hepatic JAK2/STAT3 pathway, hepatocyte replication, and liver regeneration induced by either chronic liver injury or metabolic stress. Our data suggest that hepatic NIK acts as a rheostat for liver regeneration to restrain liver overgrowth. Pathologic activation of hepatic NIK blocks hepatocyte replication, likely contributing to liver disease progression.

scholarly journals Hepatic NF-kB-inducing kinase (NIK) suppresses mouse liver regeneration in acute and chronic liver diseases

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Yi Xiong ◽  
Adriana Souza Torsoni ◽  
Feihua Wu ◽  
Hong Shen ◽  
Yan Liu ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Regeneration ◽  
Chronic Liver Disease ◽  
Disease Progression ◽  
Partial Hepatectomy ◽  
Cell Cycle Progression ◽  
Underlying Mechanism ◽  
Chronic Liver ◽  
Hepatocyte Proliferation ◽  
Liver Disease Progression

Reparative hepatocyte replication is impaired in chronic liver disease, contributing to disease progression; however, the underlying mechanism remains elusive. Here, we identify Map3k14 (also known as NIK) and its substrate Chuk (also called IKKα) as unrecognized suppressors of hepatocyte replication. Chronic liver disease is associated with aberrant activation of hepatic NIK pathways. We found that hepatocyte-specific deletion of Map3k14 or Chuk substantially accelerated mouse hepatocyte proliferation and liver regeneration following partial-hepatectomy. Hepatotoxin treatment or high fat diet feeding inhibited the ability of partial-hepatectomy to stimulate hepatocyte replication; remarkably, inactivation of hepatic NIK markedly increased reparative hepatocyte proliferation under these liver disease conditions. Mechanistically, NIK and IKKα suppressed the mitogenic JAK2/STAT3 pathway, thereby inhibiting cell cycle progression. Our data suggest that hepatic NIK and IKKα act as rheostats for liver regeneration by restraining overgrowth. Pathological activation of hepatic NIK or IKKα likely blocks hepatocyte replication, contributing to liver disease progression.

scholarly journals Acute-On-Chronic Liver Failure Defined by Asian Pacific Association for the Study of the Liver Should Include Decompensated Cirrhosis

2021 ◽  
Vol 8 ◽  
Author(s):  
Manman Xu ◽  
Ming Kong ◽  
Pengfei Yu ◽  
Yingying Cao ◽  
Fang Liu ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Failure ◽  
Chronic Liver Disease ◽  
Chronic Liver ◽  
Decompensated Cirrhosis ◽  
Chronic Liver Failure ◽  
Short Term ◽  
Asian Pacific ◽  
Long Term Mortality

Background and Aims: Acute-on-chronic liver failure (ACLF) is an acute deterioration of chronic liver disease with high short-term mortality. The inclusion or exclusion of previously decompensated cirrhosis (DC) in the diagnostic criteria of ACLF defined by the Asian Pacific Association for the Study of the Liver (APASL-ACLF) has not been conclusive. We aimed to evaluate the prognostic impact of decompensated cirrhosis in ACLF.Methods: We retrospectively collected a cohort of patients with a diagnosis of APASL-ACLF (with or without DC) hospitalized from 2012 to 2020 at three liver units in tertiary hospitals. Baseline characteristics and survival data at 28, 90, 180, 360, 540, and 720 days were collected.Results: Of the patients assessed using APASL-ACLF criteria without the diagnostic indicator of chronic liver disease, 689 patients were diagnosed with ACLF, of whom 435 had no decompensated cirrhosis (non-DC-ACLF) and 254 had previously decompensated cirrhosis (DC-ACLF). The 28-, 90-, 180-, 360-, 540-, and 720-day mortality were 24.8, 42.9, 48.7, 57.3, 63.4, and 68.1%, respectively, in DC-ACLF patients, which were significantly higher than in non-DC-ACLF patients (p < 0.05). DC was independently associated with long-term (180/360/540/720 days) but not short-term (28/90 days) mortality in patients with ACLF. Age, total bilirubin, international normalized ratio, and hepatic encephalopathy were independent risk factors for short- and long-term mortality risk in ACLF patients (p < 0.05).Conclusions: Patients with DC-ACLF have a higher mortality rate, especially long-term mortality, compared to non-DC-ACLF patients. Therefore, DC should be included in the diagnostic criteria of APASL-ACLF and treated according to the ACLF management process.

1129 SERPIN-B3 AS A PRO-FIBROGENIC MEDIATOR CONTRIBUTING TO CHRONIC LIVER DISEASE PROGRESSION

2013 ◽  
Vol 58 ◽  
pp. S460
Author(s):  
C. Paternostro ◽  
C. Busletta ◽  
C. Turato ◽  
S. Cannito ◽  
G. Villano ◽  
...  
Keyword(s):  
Liver Disease ◽  
Chronic Liver Disease ◽  
Disease Progression ◽  
Chronic Liver ◽  
Liver Disease Progression

OC-03 SERPIN-B3 as a pro-fibrogenic mediator contributing to chronic liver disease progression

2013 ◽  
Vol 45 ◽  
pp. S2
Author(s):  
C. Paternostro ◽  
C. Busletta ◽  
C. Turato ◽  
S. Cannito ◽  
A. Biasiolo ◽  
...  
Keyword(s):  
Liver Disease ◽  
Chronic Liver Disease ◽  
Disease Progression ◽  
Chronic Liver ◽  
Liver Disease Progression

scholarly journals Use of skeletal muscle index as a predictor of short-term mortality in patients with acute-on-chronic liver failure

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tongzeng Li ◽  
Manman Xu ◽  
Ming Kong ◽  
Wenyan Song ◽  
Zhongping Duan ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Liver Disease ◽  
Liver Failure ◽  
Chronic Liver Disease ◽  
Serum Bilirubin ◽  
Chronic Liver ◽  
Chronic Liver Failure ◽  
Short Term ◽  
Skeletal Muscle Index ◽  
Short Term Mortality

AbstractSarcopenia is a well-recognized factor affecting the prognosis of chronic liver disease, but its impact on acute decompensation underlying chronic liver disease is unknown. This study evaluated the impact of sarcopenia on short-term mortality in patients with acute-on-chronic liver failure (ACLF). One hundred and seventy-one ACLF patients who underwent abdominal CT between 2015 and 2019 were retrospectively included in this study. Skeletal muscle index at the third lumbar vertebrae (L3-SMI) was used to diagnose sarcopenia.The ACLF patients in this study had a L3-SMI of 41.2 ± 8.3 cm2/m2 and sarcopenia was present in 95/171 (55.6%) patients. Body mass index (BMI), cirrhosis, and higher serum bilirubin were independently associated with sarcopenia. Following multivariate Cox regression analysis, cirrhosis (hazard ratio (HR) 2.758, 95%CI 1.323–5.750), serum bilirubin (HR 1.049, 95%CI 1.026–1.073), and international normalized ratio (INR) (HR 1.725, 95%CI 1.263–2.355) were associated with 3-month mortality (P < 0.05), whereas L3-SMI and sarcopenia were not. A subgroup analysis of the factors related to sarcopenia showed that sarcopenia was still not predictive of short-term outcome in ACLF patients. L3-SMI and sarcopenia are not associated with short-term mortality in patients with ACLF.

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