Acute Kidney Injury ; etiology ; prevention & control ; Ascites ; etiology ; prevention & control ; Humans ; Hyponatremia ; etiology ; prevention & control ; Liver Cirrhosis ; complications ; prevention & control

Acute-on-chronic liver failure (ACLF) is an increasingly recognized distinct disease entity encompassing an acute deterioration of liver function in patients with chronic liver disease. Although there are no widely accepted diagnostic criteria for ACLF, the Asia.Pacific Association for the Study of the Liver (APASL) and the American Association for the Study of Liver Disease and the European Association for the Study of the Liver (AASLD/EASL) consensus definitions are commonly used. It is obvious that the APASL and the AASLD/EASL definitions are based on fundamentally different features. Two different definitions in two different parts of the world hamper the comparability of studies. Recently, the EASL-Chronic Liver Failure Consortium proposed new diagnostic criteria for ACLF based on analyses of patients with organ failure. There are areas of uncertainty in defining ACLF, such as heterogeneity of ACLF, ambiguity in qualifying underlying liver disease, argument for infection or sepsis as a precipitating event, etc. Although the exact pathogenesis of ACLF remains to be elucidated, alteration of host response to injury, infection, and unregulated inflammation play important roles. The predisposition, infection/inflammation, response, organ failure (PIRO) concept used for sepsis might be useful in describing the pathophysiology and clinical categories for ACLF. Treatment strategies are limited to organ support but better understanding of the pathophysiology is likely to lead to discovery of novel biomarkers and therapeutic strategies in the future.
Chronic Disease ; Echocardiography ; Humans ; Liver Cirrhosis/complications ; Liver Failure/diagnosis/etiology/*pathology/prevention & control ; Liver Failure, Acute/diagnosis/etiology/*pathology/prevention & control ; Liver Transplantation ; Sepsis/complications

Animals ; Drugs, Chinese Herbal ; therapeutic use ; Hepatitis B, Chronic ; complications ; Humans ; Liver Cirrhosis ; drug therapy ; etiology ; prevention & control ; Phytotherapy

Ascites ; etiology ; therapy ; Hepatorenal Syndrome ; etiology ; prevention & control ; Humans ; Hyponatremia ; etiology ; therapy ; Liver Cirrhosis ; complications ; therapy ; Sodium ; blood ; Sodium Chloride ; administration & dosage

Mesothelial cells (MCs) cover the surface of visceral organs and the parietal walls of cavities, and they synthesize lubricating fluids to create a slippery surface that facilitates movement between organs without friction. Recent studies have indicated that MCs play active roles in liver development, fibrosis, and regeneration. During liver development, the mesoderm produces MCs that form a single epithelial layer of the mesothelium. MCs exhibit an intermediate phenotype between epithelial cells and mesenchymal cells. Lineage tracing studies have indicated that during liver development, MCs act as mesenchymal progenitor cells that produce hepatic stellate cells, fibroblasts around blood vessels, and smooth muscle cells. Upon liver injury, MCs migrate inward from the liver surface and produce hepatic stellate cells or myofibroblast depending on the etiology, suggesting that MCs are the source of myofibroblasts in capsular fibrosis. Similar to the activation of hepatic stellate cells, transforming growth factor β induces the conversion of MCs into myofibroblasts. Further elucidation of the biological and molecular changes involved in MC activation and fibrogenesis will contribute to the development of novel approaches for the prevention and therapy of liver fibrosis.
Epithelial Cells/*physiology ; Epithelium/metabolism ; Hepatic Stellate Cells/*physiology ; Humans ; Liver/*cytology/injuries/*physiology ; Liver Cirrhosis/etiology/prevention & control ; Liver Regeneration/*physiology ; Mesenchymal Stromal Cells/physiology ; Myofibroblasts/physiology

OBJECTIVE: To investigate the influence of endoscopic variceal ligation (EVL) on liver function and analyze the risk factors of rebleeding after EVL. METHODS: A total of 137 cirrhotic patients with esophageal varices who received EVL were retrospectively analyzed, and divided into group A, B, and C according to the Child-Pugh scores of liver function. We compared the liver function 1 week preoperatively and postoperatively. The patients were further divided into a rebleeding group and a non-rebleeding group after the EVL, and risk factors about rebleeding were analyzed. RESULTS: There was no significant difference on ALT, AST, T-Bil, and D-Bil either preoperatively or postoperatively in group A, B, and C (P>0.05). Thirteen patients (9.49%) rebled after the EVL. The course of disease, liver function, prothrombin time, and mass ascites were the risk factors of rebleeding. CONCLUSION EVL has no obvious effect on liver function, and the course of disease, liver function, prothrombin time and mass ascites are risk factors of rebleeding after EVL.
Adult ; Endoscopy ; methods ; Esophageal and Gastric Varices ; etiology ; surgery ; Female ; Gastrointestinal Hemorrhage ; etiology ; prevention & control ; surgery ; Humans ; Ligation ; methods ; Liver ; physiopathology ; Liver Cirrhosis ; complications ; etiology ; physiopathology ; Logistic Models ; Male ; Middle Aged ; Recurrence ; Risk Factors ; Secondary Prevention

Collagen is the most excessive extracellular matrix protein in hepatic fibrosis. Activated, but not quiescent, hepatic stellate cells (HSCs) have a high level of collagen and a smooth muscle actin (alpha SMA) expression. HSCs play a key role in the pathogenesis of hepatic fibrosis. We analyzed a mechanism leading to HSC activation by evaluating the role of oxidative stress and the expression of NFkB. In vitro study HSCs were proliferated (PCNA:2% vs 68%) and activated (alpha SMA: 5% vs 78%) by ascorbate/FeSO4, and HSCs activated by type I collagen were blocked (PCNA: 97% vs 4%, a SMA: 86% vs 9%) by a-tocopherol. In vivo study means of a SMA positive cells in liver at 400 x HPF were 48.3+/-5.2 and 15.2+/-1.8 and [3H]thymidine uptake of HSC was 529.2+/-284.8 cpm and 223.0+/-86.3 cpm in control and a-tocopherol treated group respectively at 32 hours after CCl4 injection. Nuclear extracts from activated, but not from quiescent, HSCs formed a complex with the NFkB cognate oligonucleotidesand alpha-tocopherol inhibited this bindings. This study indicates that oxidative stress plays an essential role through the induction of NFkB on HSC activation.
Actins/metabolism ; Animal ; Cells, Cultured ; Extracellular Matrix Proteins/metabolism ; Liver/cytology* ; Liver Cirrhosis/prevention & control ; Liver Cirrhosis/etiology* ; Male ; NF-kappa B/metabolism* ; Oxidative Stress* ; Rats ; Rats, Sprague-Dawley ; Vitamin E/pharmacology

Adrenergic beta-Antagonists ; therapeutic use ; Antiviral Agents ; therapeutic use ; Esophageal and Gastric Varices ; etiology ; prevention & control ; Gastrointestinal Hemorrhage ; diagnosis ; etiology ; prevention & control ; Gastroscopy ; Hemostasis, Endoscopic ; methods ; Hemostatic Techniques ; Hemostatics ; therapeutic use ; Humans ; Hypertension, Portal ; complications ; Liver Cirrhosis ; complications

OBJECTIVETo evaluate the efficacy of Fuzhenghuayu capsule for the prevention of oesophageal variceal bleeding in patients with liver cirrhosis.

METHODSA multicentre randomized placebo-controlled trial was conducted. A total of 181 liver cirrhosis patients were enrolled in the study and randomly assigned to different groups according to the level of oesophageal variceal bleeding. Patients with light oesophageal varices received Fuzhenghuayu capsule or a placebo. Patients with medium to heavy oesophageal varices received either Fuzhenghuayu capsule alone, Fuzhenghuayu capsule plus propranolol, or propranolol plus a placebo. Patients with a history of oesophageal variceal bleeding received either Fuzhenghuayu capsule plus propranolol, propranolol alone, or a placebo. For all patients, the treatment lasted 2 years. The primary end point of the study was oesophageal variceal bleeding. The secondary end points were liver cancer, death by any cause, and liver transplantation. Risk of bleeding and survival were statistically assessed.

RESULTSThe median follow-up time was 50 months. The patients with small oesophageal varices who were treated with Fuzhenghuayu capsule showed a significantly higher cumulative probability of bleeding than their counterparts treated with the placebo (3.4% vs. 23.7%, x² = 4.829, P =0.028). The patients with medium to heavy oesophageal varices and no history of oesophageal variceal bleeding who were treated with Fuzhenghuayu capsule plus propranolol showed a remarkably higher cumulative probability of bleeding than their counterparts treated with propranolol alone (15.2% vs. 43.6%, x² =6.166, P =0.013). There were no significant differences between the patients treated with Fuzhenghuayu capsule alone and those treated with propranolol alone (P =0.147) or the patients treated with Fuzhenghuayu capsule plus propranolol and those treated with Fuzhenghuayu capsule alone (P =0.147). The patients with history of oesophageal variceal bleeding who were treated with Fuzhenghuayu capsule showed significantly higher cumulative probability of bleeding and median time of bleeding than their counterparts treated with propranolol alone (44.0% vs. 24.2% and 40.00 ± 17.92 months vs. 7.00 ± 2.35 months; x² = 4.433, P =0.035). There were no significant differences in the cumulative probability of liver cancer and survival among all of the groups.

CONCLUSIONFuzhenghuayu capsule can decrease the cumulative probability of bleeding in cirrhotic patients with light oesophageal varices. For cirrhosis patients with a history of oesophageal variceal bleeding, the combination of Fuzhenghuayu capsule plus propranolol can decrease the cumulative probability of bleeding with median or heavy varices.

Adult ; Double-Blind Method ; Drugs, Chinese Herbal ; therapeutic use ; Esophageal and Gastric Varices ; etiology ; prevention & control ; Female ; Gastrointestinal Hemorrhage ; etiology ; prevention & control ; Humans ; Liver Cirrhosis ; complications ; drug therapy ; Male ; Middle Aged ; Phytotherapy ; Prospective Studies ; Treatment Outcome

A major cause of cirrhosis related morbidity and mortality is the development of variceal bleeding, a direct consequence of portal hypertension. Less common causes of gastrointestinal bleeding are peptic ulcers, malignancy, angiodysplasia, etc. Upper gastrointestinal bleeding has been classified according to the presence of a variceal or non-variceal bleeding. Although non-variceal gastrointestinal bleeding is not common in cirrhotic patients, gastroduodenal ulcers may develop as often as non-cirrhotic patients. Ulcers in cirrhotic patients may be more severe and less frequently associated with chronic intake of non-steroidal anti-inflammatory drugs, and may require more frequently endoscopic treatment. Portal hypertensive gastropathy (PHG) refers to changes in the mucosa of the stomach in patients with portal hypertension. Patients with portal hypertension may experience bleeding from the stomach, and pharmacologic or radiologic interventional procedure may be useful in preventing re-bleeding from PHG. Gastric antral vascular ectasia (GAVE) seems to be different disease entity from PHG, and endoscopic ablation can be the first-line treatment.
Gastric Antral Vascular Ectasia/complications ; Gastric Mucosa/pathology ; Gastrointestinal Hemorrhage/*etiology ; Humans ; Hypertension, Portal/*complications/prevention & control ; Liver Cirrhosis/complications ; Peptic Ulcer/complications