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The liver is a vertebrate organ that detoxifies metabolites, synthesizes proteins, and produces biochemical substances necessary for digestion. The liver is mostly consisted of hepatocytes, regulating biochemical reactions necessary for normal life function. In the conditions of liver insufficiency, toxins could accumulate in the plasma and cause progressive encephalopathy and multiorgan dysfunction. Complications such as hyperdynamic circulation, coagulopathy failure, acute renal and respiratory insufficiency, cerebral edema, which will finally lead to brain death. Artificial liver support systems are designed to replace the detoxification functions in the liver temporally. With some artificial liver support systems, albumin is used as scavenger molecules for clearing toxins. Many studies observed that patients who received an artificial liver support system had significantly higher transplant-free survival than those who have not. Basically, artificial liver can act as “bridge” to the transplant procedure.

Various hepatoxic factors, such as viruses, drugs, lipid deposition, and autoimmune responses, induce acute or chronic liver injury, and 3.5% of all worldwide deaths result from liver cirrhosis, liver failure, or hepatocellular carcinoma. Liver transplantation is currently limited by few liver donors, expensive surgical costs, and severe immune rejection. Cell therapy, including hepatocyte transplantation and stem cell transplantation, has recently become an attractive option to reduce the overall need for liver transplantation and reduce the wait time for patients. Recent studies showed that mesenchymal stem cell (MSC) administration was a promising therapeutic approach for promoting liver regeneration and repairing liver injury by the migration of cells into liver sites, hepatogenic differentiation, immunoregulation, and paracrine mechanisms. MSCs secrete a large number of molecules into the extracellular space, and soluble proteins, free nucleic acids, lipids, and extracellular vesicles (EVs) effectively repair tissue injury in response to fluctuations in physiological states or pathological conditions. Cell-free-based therapies avoid the potential tumorigenicity, rejection of cells, emboli formation, undesired differentiation, and infection transmission of MSC transplantation. In this review, we focus on the potential mechanisms of MSC-based cell-free strategies for attenuating liver injury in various liver diseases. Secretome-mediated paracrine effects participate in the regulation of the hepatic immune microenvironment and promotion of hepatic epithelial repair. We look forward to completely reversing liver injury through an MSC-based cell-free strategy in regenerative medicine in the near future.

BACKGROUND AND AIMS It is controversial whether patients with cirrhosis benefit from the intensive care unit (ICU) management. To identify the patients in whom ICU care may offer recovery, this study aimed to determine specific risk factors and to establish a novel prognostic score for 3-month mortality in critically ill patients with cirrhosis. METHODS An observational study was performed from August 2008 to May 2014, encompassing 349 critically ill patients with cirrhosis during their ICU stay (a 70% training and 30% validation set). RESULTS The overall 3-month mortality rate was 68.1% in training cohort. Prothrombin time, serum bilirubin, use of vasopressors, hepatic encephalopathy, and systemic inflammatory response syndrome at admission were identified as being strongly correlated with the 3-month prognosis. Based on these five variables, a modified score for critically ill cirrhosis (MSCIC) was developed. An increasing MSCIC was significantly correlated with a reduction in the rate of survival (P

Background Systematic analysis of histopathological and serial virological changes of fatal influenza A(H7N9) cases is lacking. Methods Patients with A(H7N9) infection admitted to our intensive care unit during 10-23 April 2013 were included. Viral loads in the respiratory tract, as inferred from the cycle threshold (Ct) value of reverse transcription polymerase chain reaction (RT-PCR), and the serum hemagglutination inhibition (HAI) antibody titer, were analyzed. Postmortem biopsies of the lung, liver, kidney, spleen, bone marrow, and heart were examined. Results Twelve patients (6 deaths, 6 survivors) were included. Median viral load was higher in sputa than the nasopharyngeal swabs for fatal cases (median Ct, 23 vs 30.5; P = .08). RT-PCR for A(H7N9) was positive in stool samples (4/6 [67%]) of fatal cases and (2/6 [33%]) of survivors, but was negative in the cerebrospinal fluid, urine, or blood of all patients. Nosocomial bacterial infections were more common in patients who died than in survivors (83% vs 50%). HAI titers increased by ≥4-fold in those with convalescent sera. Postmortem biopsy for 3 patients showed acute diffuse alveolar damage. Patient 1, who died 8 days after symptom onset, had intra-alveolar hemorrhage. Patients 2 and 3, who died 11 days after symptom onset, had pulmonary fibroproliferative changes. Reactive hemophagocytosis in the bone marrow and lymphoid atrophy in splenic tissues were compatible with laboratory findings of leukopenia, lymphopenia, and thrombocytopenia. Hypoxic and fatty changes of kidney and liver tissues are compatible with impaired renal or liver function. Conclusions Fatal A(H7N9) infection was characterized by viral and secondary bacterial pneumonia with 67% having positive RT-PCR in stool.

Increasing evidence suggests a role of intestinal dysbiosis in obesity and non-alcoholic fatty liver disease (NAFLD). But it remains unknown in nonobese NAFLD. This prospective, cross-sectional study sought to characterize differences in fecal microbiota between nonobese adult individuals with and without NAFLD and their potential association with metabolic markers of disease progression. A total of 126 nonobese subjects were enrolled: 43 NAFLD and 83 healthy controls (HC). The microbial community was profiled by denaturing gradient gel electrophoresis and examined by 454 pyrosequencing of the 16S ribosomal RNA V3 region. Lower diversity and a phylum-level change in the fecal microbiome were found in NAFLD. Compared with HC, patients had 20% more phylum Bacteroidetes (p = 0.005) and 24% less Firmicutes (p = 0.002). Within Firmicutes, four families and their 8 genera, which were short-chain fatty acids-producing and 7α-dehydroxylating bacteria, were significantly decreased. Moreover, Gram-negative (G−) bacteria were prevalent in NAFLD (p = 0.008). Furthermore, a significant correlation with metabolic markers was revealed for disturbed microbiota in NAFLD. This novel study indicated that intestinal dysbiosis was associated with nonobese NAFLD and might increase the risk of NAFLD progression.

Background A novel avian-origin influenza A (H7N9) virus emerged and spread among humans in Eastern China in 2013. Prophylactic treatment with antibiotics and probiotics for secondary infection is as important as antiviral treatment. This study aims to assess the ability of probiotic treatment to restore internal homeostasis under antibiotic pressure and to reduce/ameliorate the risk of secondary infections resulting from infection with the H7N9 virus. Methods This is a retrospective study in archival samples. Between April 1 and May 10, 2013, 113 stool, sputum, and blood specimens were collected and analyzed by denaturing gradient gel electrophoresis (DGGE) to determine the composition of the patient microbiomes. Microbial diversity was calculated using Gel-Pro analyzer and Past software. Cluster analysis of DGGE pattern profiles was employed to create a phylogenetic tree for each patient, and multidimensional scaling (MDS) and principal component analysis (PCA) were performed to visualize relationships between individual lanes. Results Five patients had secondary infections, including Klebsiella pneumonia, Acinetobacter baumanii and Candida albicans infection. The DGGE profiles of fecal samples obtained at different time points from the same individual were clearly different, particularly for patients with secondary infections. Shannon’s diversity index and evenness index were lower in all infected groups compared to the control group. After B. subtilis and E. faecium or C. butyricum administration, the fecal bacterial profiles of patients who had not been treated with antibiotics displayed a trend of increasing diversity and evenness. C. butyricum failed to reduce/ameliorate secondary infection in H7N9-infected patients, but administration of B. subtilis and E. faecium appeared to reduce/ameliorate secondary infection in one patient. Conclusion H7N9 infection might decrease intestinal microbial diversity and species richness in humans. C. butyricum failed to reduce/ameliorate secondary infection in H7N9-infected patients. B. subtilis and E. faecium may also play a role in reducing/ameliorating secondary infection in these patients.

It is controversial whether patients with cirrhosis benefit from the intensive care unit (ICU) management. To identify the patients in whom ICU care may offer recovery, this study aimed to determine specific risk factors and to establish a novel prognostic score for 3-month mortality in critically ill patients with cirrhosis.An observational study was performed from August 2008 to May 2014, encompassing 349 critically ill patients with cirrhosis during their ICU stay (a 70% training and 30% validation set).The overall 3-month mortality rate was 68.1% in training cohort. Prothrombin time, serum bilirubin, use of vasopressors, hepatic encephalopathy, and systemic inflammatory response syndrome at admission were identified as being strongly correlated with the 3-month prognosis. Based on these five variables, a modified score for critically ill cirrhosis (MSCIC) was developed. An increasing MSCIC was significantly correlated with a reduction in the rate of survival (P 0.001). Moreover, excellent predictive power was found when the MSCIC was used (area under the receiver operating characteristic curve: 0.856 ± 0.047), which was significantly better than the prognostic efficiency of Acute Physiology and Chronic Health Evaluation II (P 0.001), Model for End-stage Liver Disease (P = 0.02), Simplified Acute Physiology Score (P = 0.023), and the Child-Turcotte-Pugh score (P = 0.01); the MSCIC score was slightly better than that of Chronic Liver Failure-Sequential Organ Failure Assessment (P = 0.068). The similar result was obtained in validation set.The MSCIC is an easily adopted tool with a high prognostic efficacy for patients with advanced cirrhosis; MSCIC may act as a supplement to the clinical judgment of physicians when considering the prognosis.