Changes in portal hemodynamics after TIPS in liver cirrhosis and portal hypertension.

OBJECTIVE: The objective of this study is to analyze the changes in portal hemodynamics that occurs in portal hypertension before and after transjugular intrahepatic portosystemic shunt (TIPS), to investigate the relationship between these changes and portal pressure (PP) and to determine the significance of sonographic parameters in measuring PP. METHODS: Ultrasonography of the portal and splenic veins and direct measurement of the PP were performed in 92 patients before and after TIPS. The differences observed in the portal and splenic vein diameters, the blood flow velocity in the portal and splenic veins and the PP were measured, and the correlations between PP and the other parameters were assessed using the SPSS 13 (SPSS Inc., Chicago, IL, USA). P < 0.05 was considered statistically significant. RESULTS: We observed a significant decrease in the PP and the diameters of the portal and splenic veins compared to preoperative conditions (p < 0.001). The velocity of blood flow in the portal and splenic veins was significantly increased after TIPS (p < 0.001). The PP correlated with the diameter and velocity of blood flow in portal (r = 0.46, p = 0.020; r = 0.47, p = 0.017) and splenic vein (r = 0.57, p = 0.003; r = 0.33, p = 0.003) only in Child's A and was absent in Child's B cirrhosis patients. CONCLUSION: The PP is influenced by the complex interaction between intrahepatic vascular resistance, collaterals and the amount of portal blood flow, which varies considerably between individuals. Once a certain pressure threshold is reached, collaterals form, and the correlation between the ultrasonographic parameters and PP becomes limited.

Transjugular intrahepatic portosystemic shunt vs endoscopic therapy in preventing variceal rebleeding.

AIM: To compare early use of transjugular intrahepatic portosystemic shunt (TIPS) with endoscopic treatment (ET) for the prophylaxis of recurrent variceal bleeding. METHODS: In-patient data were collected from 190 patients between January 2007 and June 2010 who suffured from variceal bleeding. Patients who were older than 75 years; previously received surgical treatment or endoscopic therapy for variceal bleeding; and complicated with hepatic encephalopathy or hepatic cancer, were excluded from this research. Thirty-five cases lost to follow-up were also excluded. Retrospective analysis was done in 126 eligible cases. Among them, 64 patients received TIPS (TIPS group) while 62 patients received endoscopic therapy (ET group). The relevant data were collected by patient review or telephone calls. The occurrence of rebleeding, hepatic encephalopathy or other complications, survival rate and cost of treatment were compared between the two groups. RESULTS: During the follow-up period (median, 20.7 and 18.7 mo in TIPS and ET groups, respectively), rebleeding from any source occurred in 11 patients in the TIPS group as compared with 31 patients in the ET group (Kaplan-Meier analysis and log-rank test, P = 0.000). Rebleeding rates at any time point (6 wk, 1 year and 2 year) in the TIPS group were lower than in the ET group (Bonferroni correction α' = α/3). Eight patients in the TIPS group and 16 in the ET group died with the cumulative survival rates of 80.6% and 64.9% (Kaplan-Meier analysis and log-rank test χ(2) = 4.864, P = 0.02), respectively. There was no significant difference between the two groups with respect to 6-wk survival rates (Bonferroni correction α' = α/3). However, significant differences were observed between the two groups in the 1-year survival rates (92% and 79%) and the 2-year survival rates (89% and 64.9%) (Bonferroni correction α' = α/3). No significant differences were observed between the two treatment groups in the occurrence of hepatic encephalopathy (12 patients in TIPS group and 5 in ET group, Kaplan-Meier analysis and log-rank test, χ(2) = 3.103, P = 0.08). The average total cost for the TIPS group was higher than for ET group (Wilcxon-Mann Whitney test, 52 678 RMB vs 38,844 RMB, P < 0.05), but hospitalization frequency and hospital stay during follow-up period were lower (Wilcxon-Mann Whitney test, 0.4 d vs 1.3 d, P = 0.01; 5 d vs 19 d, P < 0.05). CONCLUSION: Early use of TIPS is more effective than endoscopic treatment in preventing variceal rebleeding and improving survival rate, and does not increase occurrence of hepatic encephalopathy.

Follow-up study of transjugular intrahepatic portosystemic shunt in the treatment of portal hypertension.

OBJECTIVE: To evaluate efficacy and complications for cirrhotic patients with variceal bleeding receiving TIPS. METHODS: Of 137 patients who underwent TIPS from 2002 to 2009, 80 patients were included in this study. Information about the incidence of portosystemic encephalopathy (PSE) and rebleeding, and factors then which affected them, was collected by telephone call, letters, or follow-up visits in the out-patient department. RESULTS: (1) TIPS can significantly reduce portal pressure and the risk of variceal bleeding. (2) A coated stent during TIPS can significantly reduce the occurrence of rebleeding in contrast with use of a bare stent (13.51% vs. 32.56%, P < 0.05). (3) Incidence of PSE is related to the diameter of the stent; the wider the stent used, the greater the incidence of PSE. TIPS using the left branch of the portal vein can reduce the incidence of PSE. (4) TIPS combined with embolization has no effect on the incidence of rebleeding or PSE. (5) Mean survival was 77.098 months (95% CI, 68.568-85.628) and median survival 82.000 months (95% CI, 68.539-95.461) according to Kaplan-Meier survival analysis. CONCLUSION: It is suggested that coated stents should be used to reduce rebleeding. It is recommended that 8 mm stents should be used for CHILD A and C patients and 8-10 mm stents for CHILD B patients during TIPS, and that TIPS should be considered as first-line therapy because it improves cumulative survival for cirrhotic patients with gastroesophageal variceal bleeding.

The inhibitory effect of polypeptide cSN50 on alcoholic hepatic injuries through blocking the binding of NF-κB to importin α.

OBJECTIVE: To study whether alcohol and endotoxin induce inflammation, apoptosis, and expression of downstream genes TNF-α and caspase-3 through the nuclear transcription factor NF-κB, i.e., the IκB-NF-κB-importin α pathway. METHODS: Flow cytometry was used to observe the apoptosis rate in human hepatoma cells (HepG(2)) and murine macrophages (RAW264.7) after being stimulated by alcohol and endotoxin at different concentrations. The caspase-3 activity was determined by spectrophotometry and TNF-α level in cell culture supernatant by ELISA. Western blot was used to examine the expression level of P50, importin α3 and IκBα, and indirect immunofluorescence to determine the activation level of P50, importin α3 and IκBα. RESULTS: In human hepatoma cells, a transmembrane polypeptide, cSN50, inhibited the elevation in the level of TNF-α and caspase-3 and the expression of nuclear transport receptor importin α3 stimulated by alcohol and endotoxin. Immunofluorescence showed the nuclear translocation of NF-κB and importin α3 and cytosolic degradation of IκBα. In murine mononuclear macrophages, addition of alcohol or endotoxin or both resulted in a significant elevation of NF-κB and its downstream factors TNF-α and caspase-3 and apoptosis of RAW264.7 cells. These effects were remarkably suppressed by cSN50. However, the expression of importin α3 was not detected by Western blotting or immunofluorescence in this experiment, indicating the existence of other pathways. CONCLUSION: The nuclear translocation of NF-κB plays an important role in acute alcoholic hepatic injuries and the induced nuclear NF-κB activity, and its downstream gene expression can be partially suppressed by cSN50 in HepG(2) and RAW264.7 cells.

Emerging role of resveratrol in the treatment of severe acute pancreatitis.

Severe acute pancreatitis (SAP) develops in 15-20% of patients with acute pancreatitis. The management of SAP is a challenging task owing to the fact that it can lead to morbid conditions like multiple organ failure and systemic inflammatory response syndrome, if left untreated. Resveratrol, a drug used in Chinese traditional medicine has shown potential to treat many symptoms of SAP due to its multiple physiological actions. It possesses anti-inflammatory and anti-oxidative properties, both of which are essential in SAP. NF-kappaB activation is a major source of pro-inflammatory mediators in SAP. Administration of resveratrol can inhibit NF-kappaB activity as well as reduce the concentrations of TNF-alpha, IL-6 and IL-1. It can also scavenge reactive oxygen species that are capable of extensive tissue damage. Furthermore, resveratrol also exhibits anti-apoptotic properties via regulation of apoptotic mediators such as Bax, Bcl-2, and caspase-3. It also plays a role in calcium regulation and alleviates SAP-induced histopathological distortions in the pancreas. These multi-faceted results support the use of resveratrol in SAP and mandate the need for extensive research on this molecule.

The role of intravascular intervention in the management of Budd-Chiari syndrome.

OBJECTIVE: To evaluate the efficacy of intravascular intervention in the management of different types of Budd-Chiari syndrome. METHODS: Fifty-three patients of BCS were clinically diagnosed and interventionally treated in terms of their signs and symptoms of portal hypertension and occlusive inferior vena cava/or hepatic veins with the combination of Doppler ultrasonography, CT scan, and angiography. The interventional methods applied in this study included percutaneous transluminal angioplasty and IVC stent implantation (PTA+IVC stent); transjugular hepatic veno-stent placement (PTA+HV stent) or transjugular transluminal hepatic veno-inferior vena cava stent placement and transcaval transjugular intrahepatic portocaval shunt. RESULTS: The success rate of intravascular interventional therapy was 92.45% (49/53). After interventional therapy, the patients' pleural effusion, ascites, prominent veins formation of bilateral flanks or backs alleviated, hepatomegaly reduced, and the urinary output increased. The longest follow-up case was 13 years with patent stent. Two patients died of pulmonary embolization or pericardial tamponade during surgery. CONCLUSION: Intravascular intervention is a safe and effective therapy for most types of BCS.

Protective effect of resveratrol in severe acute pancreatitis-induced brain injury.

OBJECTIVES: The aim of this study was to study the effects of resveratrol on severe acute pancreatitis (SAP)-induced brain injury. METHODS: Ninety-six male Sprague-Dawley rats were randomly divided into 4 equal groups: sham operation, SAP, resveratrol-treated (RES), and dexamethasone-treated. Each group was evaluated at 3, 6, and 12 hours. Levels of serum myelin basic protein and zonula occludens 1 (Zo-1) were determined by enzyme-linked immunosorbent assay. The brain and pancreatic tissues were examined using electron microscopy. Expressions of Bax, Bcl-2, and caspase-3 were observed using immunohistochemistry, reverse transcriptase polymerase chain reaction, and Western blotting. Cytochrome c was detected using Western blotting alone. RESULTS: Myelin basic protein and Zo-1 levels of the RES group were lower than the SAP group at all time points (P < 0.05). The RES group had significantly improved pathologic brain, increase in Bcl-2 expression, and decrease in Bax and caspases-3 expressions compared with the SAP group. CONCLUSIONS: The degradation of Zo-1 is involved in the pathophysiology of brain injury in SAP; MBP can be used as a marker of brain injury in SAP. The protective effect of resveratrol might be associated with the up-regulation of Bcl-2 and down-regulation of Bax and caspase-3.

Acute pancreatitis: a literature review.

Acute pancreatitis (AP) is an inflammatory disease characterized by steady, acute abdominal pain of varying severity, often radiating from the epigastrium to the back. Its presentation ranges from a self-limiting mild disorder to a more severe and fulminant disease. Severe acute pancreatitis accounts for 30% of all deaths related to pancreatitis. The incidence of AP is increasing progressively with a corresponding increase in the incidence of its risk factors. Alcohol abuse and gallstone migration are the established risk factors for development of AP. In recent years, genetic factors and obesity have also been identified as risk factors responsible for the development of AP. The pathophysiology of AP involves acute inflammation of the acinar cells. Excessive acinar cell injury leads to a condition called systemic inflammatory response syndrome (SIRS). Protracted SIRS is responsible for most of the life-threatening complications associated with AP. Most common AP-related complications include pulmonary, renal, cardiovascular, and central nervous system dysfunction. Thus prompt and accurate diagnosis of AP is of paramount importance. The medical management of AP includes controlling pain, providing adequate nutritional support, and monitoring complications. Endoscopic retrograde cholangiopancreatography and surgery have also shown to reduce the mortality and morbidity associated with AP. Drugs such as resveratrol and rosiglitazone are being investigated as potential candidates for the treatment of AP.