Hepatoprotective Effect of MMP-19 Deficiency in a Mouse Model of Chronic Liver Fibrosis

Background: Chronic liver damages from viral infection or alcohol abuse result in liver fibrosis, which is a key pathological event in many types of liver diseases. Discovering new anti-fibrosis agents may provide alternative solutions to manage chronic liver diseases. Methods: We first used CCl4 induced liver fibrosis animal model to evaluate the beneficial effects of Cryptotanshinone (CRY). We next explored target miRNAs regulated by CRY in hepatocytes using microarray. The target miRNA candidate was confirmed with realtime-PCR. We also elucidated the downstream target and pathway directly regulated by the miRNA using luciferase assay, western blotting and Epithelial–Mesenchymal Transition (EMT) markers quantification. Lastly, we confirmed CRY induced expression changes of the target genes in vivo. Results: CRY oral administration markedly alleviated the liver injury caused by CCl4. miRNAs expression profiling and realtime-PCR validation revealed miR-539-3p was directly induced by CRY around 4 folds. The induction of miR-539-3p suppressed SMO expression and antagonized Hedgehog (Hh) pathway. Independently CRY treatment suppressed SMO and inhibited EMT process in hepatocytes. The CRY induced expression changes of both miR-539-3p (~ 2 folds increase) and SMO (~ 60% decrease) in livers were validated in animal model. Conclusion: Our study supported CRY could inhibit liver fibrosis by targeting Hh pathway during EMT. CRY could be used as anti-fibrosis agent candidate for managing chronic liver damages.

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Mac‐2 Binding Protein Glycan Isomer as non‐invasive tool to assess liver fibrosis in children with chronic liver disease

Hepatology Research ◽

10.1111/hepr.13608 ◽

2021 ◽

Author(s):

Ola G Behairy ◽

Soha A El‐Gendy ◽

Dalia Y Ibrahim ◽

Amira I Mansour ◽

Ola S El‐Shimi

Keyword(s):

Liver Disease ◽

Liver Fibrosis ◽

Chronic Liver Disease ◽

Binding Protein ◽

Chronic Liver ◽

Non Invasive

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Possible unrecognised liver injury is associated with mortality in critically ill COVID-19 patients

Therapeutic Advances in Gastroenterology ◽

10.1177/17562848211023410 ◽

2021 ◽

Vol 14 ◽

pp. 175628482110234

Author(s):

Mario Romero-Cristóbal ◽

Ana Clemente-Sánchez ◽

Patricia Piñeiro ◽

Jamil Cedeño ◽

Laura Rayón ◽

...

Keyword(s):

Liver Disease ◽

Liver Fibrosis ◽

Liver Injury ◽

Chronic Liver Disease ◽

Critically Ill ◽

Cox Regression ◽

Chronic Liver ◽

Cox Regression Analysis ◽

Risk Of Death ◽

The Impact

Background: Coronavirus disease (COVID-19) with acute respiratory distress syndrome is a life-threatening condition. A previous diagnosis of chronic liver disease is associated with poorer outcomes. Nevertheless, the impact of silent liver injury has not been investigated. We aimed to explore the association of pre-admission liver fibrosis indices with the prognosis of critically ill COVID-19 patients. Methods: The work presented was an observational study in 214 patients with COVID-19 consecutively admitted to the intensive care unit (ICU). Pre-admission liver fibrosis indices were calculated. In-hospital mortality and predictive factors were explored with Kaplan–Meier and Cox regression analysis. Results: The mean age was 59.58 (13.79) years; 16 patients (7.48%) had previously recognised chronic liver disease. Up to 78.84% of patients according to Forns, and 45.76% according to FIB-4, had more than minimal fibrosis. Fibrosis indices were higher in non-survivors [Forns: 6.04 (1.42) versus 4.99 (1.58), p < 0.001; FIB-4: 1.77 (1.17) versus 1.41 (0.91), p = 0.020)], but no differences were found in liver biochemistry parameters. Patients with any degree of fibrosis either by Forns or FIB-4 had a higher mortality, which increased according to the severity of fibrosis ( p < 0.05 for both indexes). Both Forns [HR 1.41 (1.11–1.81); p = 0.006] and FIB-4 [HR 1.31 (0.99–1.72); p = 0.051] were independently related to survival after adjusting for the Charlson comorbidity index, APACHE II, and ferritin. Conclusion: Unrecognised liver fibrosis, assessed by serological tests prior to admission, is independently associated with a higher risk of death in patients with severe COVID-19 admitted to the ICU.

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The Role of the Gut Microbiome in Liver Cirrhosis Treatment

International Journal of Molecular Sciences ◽

10.3390/ijms22010199 ◽

2020 ◽

Vol 22 (1) ◽

pp. 199

Author(s):

Na Young Lee ◽

Ki Tae Suk

Keyword(s):

Liver Cirrhosis ◽

Liver Disease ◽

Liver Fibrosis ◽

Gut Microbiota ◽

Gut Microbiome ◽

Liver Diseases ◽

Sclerosing Cholangitis ◽

Chronic Liver ◽

Chronic Liver Diseases

Liver cirrhosis is one of the most prevalent chronic liver diseases worldwide. In addition to viral hepatitis, diseases such as steatohepatitis, autoimmune hepatitis, sclerosing cholangitis and Wilson’s disease can also lead to cirrhosis. Moreover, alcohol can cause cirrhosis on its own and exacerbate chronic liver disease of other causes. The treatment of cirrhosis can be divided into addressing the cause of cirrhosis and reversing liver fibrosis. To this date, there is still no clear consensus on the treatment of cirrhosis. Recently, there has been a lot of interest in potential treatments that modulate the gut microbiota and gut-liver axis for the treatment of cirrhosis. According to recent studies, modulation of the gut microbiome by probiotics ameliorates the progression of liver disease. The precise mechanism for relieving cirrhosis via gut microbial modulation has not been identified. This paper summarizes the role and effects of the gut microbiome in cirrhosis based on experimental and clinical studies on absorbable antibiotics, probiotics, prebiotics, and synbiotics. Moreover, it provides evidence of a relationship between the gut microbiome and liver fibrosis.

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