Ying-Wen Wang

Model for end-stage liver disease score to serum sodium ratio index as a prognostic predictor and its correlation with portal pressure in patients with liver cirrhosis

Background: The models for end‐stage liver disease (MELD) and serum sodium (SNa) are important prognostic markers in cirrhosis. A novel index, MELD to SNa ratio (MESO), was developed to amplify the opposing effect of MELD and SNa on outcome prediction.

Correlation and comparison of the model for end-stage liver disease, portal pressure, and serum sodium for outcome prediction in patients with liver cirrhosis.

Background The model for end-stage liver disease (MELD), hepatic venous pressure gradient (HVPG), and serum sodium (SNa) are important prognostic markers for patients with liver cirrhosis. The correlation among these markers and their predictive accuracy for survival are unclear. Methods A total of 213 cirrhotic patients undergoing hemodynamic measurement were analyzed. The correlations between MELD score, SNa, and hemodynamic parameters were investigated. Results There was a significant correlation between MELD and HVPG (r=0.255, P<0.001), between SNa and MELD (r=−0.483, P<0.001), and between HVPG and SNa (r=−0.213, P=0.002). Using mortality as the end-point, the area under receiver operating characteristic curve (AUC) for MELD was 0.789, compared with 0.659 for HVPG (P=0.165) and 0.860 for SNa (P=0.34) at 3 months; the difference between HVPG and SNa was significant (P=0.015). The AUC at 6 months was significantly higher for SNa and MELD compared with that of HVPG. Among 134 patients with low (<14) MELD scores, a high (>16 mm Hg) HVPG, and low SNa (<135 mEq/L) predicted early mortality. In the Cox multivariate model, MELD, HVPG, and Child-Turcotte-Pugh scores were consistently identified as independent poor prognostic predictors when they were treated either as dichotomous or continuous variables in the model. Conclusions MELD score is closely associated with HVPG and SNa in cirrhotic patients. HVPG is not superior to MELD score or SNa for short-term outcome prediction. High HVPG and low SNa may identify high-risk patients with low MELD scores. High MELD, HVPG, and Child-Turcotte-Pugh scores are independent predictors of poor long-term survival.

Multiple effects of honokiol on the life cycle of hepatitis C virus

Honokiol, a small active molecular compound extracted from magnolia, has recently been shown to inhibit hepatitis C virus (HCV) infection in vitro.

Effects of N-acetylcysteine administration in hepatic microcirculation of rats with biliary cirrhosis

BACKGROUND/AIMS Increased intrahepatic resistance (IHR) in cirrhosis is due to fibrosis and hepatic endothelial dysfunction (HED). Besides producing fibrosis, increased reactive oxygen species (ROS) promotes ROS-related nitration of anti-oxidative enzymes in cirrhotic livers. Tyrosine nitration (nitrotyrosilation)-related inactivation of anti-oxidative enzymes is increased in cirrhotic livers. This study investigates effects of N-acetylcysteine (NAC) administrations in bile-duct-ligation (BDL) rats. METHODS This study measured portal venous pressure (PVP), IHR, hepatic endothelial function, hepatic levels of anti-oxidants and oxidants, type III procollagen (PIIIP), proteins expression of thromboxane synthase (TXS), nitrotyrosine, manganese superoxide dismutase (MnSOD), and hepatic NOx and thromboxane A(2) (TXA(2)) production in perfusates. RESULTS The improvement of HED was associated with decreased PVP and IHR, hepatic protein and mRNA levels of PIIIP, protein expression of TXS and nitrotyrosine, oxidants and production of TXA(2) in NAC-treated BDL rat livers. Conversely, hepatic NOx production, anti-oxidants, and protein expression of MnSOD were increased in NAC-treated BDL rat livers. CONCLUSIONS In NAC-treated cirrhotic rats, the decrease in IHR was mainly caused by its anti-oxidative effect-related prevention of hepatic fibrogenesis associated with the decrease of oxidants-related nitrotyrosilation and improvement of HED.

Sildenafil decreased pulmonary arterial pressure but may have exacerbated portal hypertension in a patient with cirrhosis and portopulmonary hypertension

Portopulmonary hypertension is a recognized but uncommon complication of cirrhosis. Liver transplantation may be contraindicated in patients with severe portopulmonary hypertension. In order to decrease the pulmonary arterial pressure, intravenous administration of epoprostenol has been shown to provide substantial beneficial results in these patients. Additionally, a recent case report demonstrated that long-term oral administration of sildenafil decreased pulmonary arterial pressure, but its effects on splanchnic hemodynamics were not measured. We report on a patient with cirrhosis and portopulmonary hypertension and the changes in the hemodynamic status after an oral administration of sildenafil. This case report clearly delineates that sildenafil decreases pulmonary arterial pressure but may exacerbate portal hypertension and hyperdynamic circulation in patients with cirrhosis and portopulmonary hypertension.

Effect of chronic CB1 cannabinoid receptor antagonism on livers of rats with biliary cirrhosis

Recent studies have shown that the activated endocannabinoid system participates in the increase in IHR (intrahepatic resistance) in cirrhosis. The increased hepatic production of vasoconstrictive eicosanoids is involved in the effect of endocannabinoids on the hepatic microcirculation in cirrhosis; however, the mechanisms of these effects are still unknown. The aim of the present study was to investigate the effects of chronic CB(1) (cannabinoid 1) receptor blockade in the hepatic microcirculation of CBL (common bile-duct-ligated) cirrhotic rats. After 1 week of treatment with AM251, a specific CB(1) receptor antagonist, IHR, SMA (superior mesenteric artery) blood flow and hepatic production of eicosanoids [TXB(2) (thromboxane B(2)), 6-keto PGF(1alpha) (prostaglandin F(1alpha)) and Cys-LTs (cysteinyl leukotrienes)] were measured. Additionally, the protein levels of hepatic COX (cyclo-oxygenase) isoforms, 5-LOX (5-lipoxygenase), CB(1) receptor, TGF-beta(1) (transforming growth factor beta(1)), cPLA(2) [cytosolic PLA(2) (phospholipase A(2))], sPLA(2) (secreted PLA(2)) and collagen deposition were also measured. In AM251-treated cirrhotic rats, a decrease in portal venous pressure was associated with the decrease in IHR and SMA blood flow. Additionally, the protein levels of hepatic CB(1) receptor, TGF-beta(1), cPLA(2) and hepatic collagen deposition, and the hepatic levels of 5-LOX and COX-2 and the corresponding production of TXB(2) and Cys-LTs in perfusates, were significantly decreased after 1 week of AM251 treatment in cirrhotic rats. Furthermore, acute infusion of AM251 resulted in a decrease in SMA blood flow and an increase in SMA resistance in CBL rats. In conclusion, the chronic effects of AM251 treatment on the intrahepatic microcirculation were, at least partly, mediated by the inhibition of hepatic TGF-beta(1) activity, which was associated with decreased hepatic collagen deposition and the activated PLA(2)/eicosanoid cascade in cirrhotic livers.

Role of Ca2+-dependent potassium channels in in vitro anandamide-mediated mesenteric vasorelaxation in rats with biliary cirrhosis

Background/Aim: Anandamide can activate potassium (K+) channels to induce an endothelium‐dependent vasorelaxation in normal rat mesenteric arteries. Cannabinoids contribute partly to the splanchnic vasodilation in cirrhosis. This study investigated the roles of vascular K+ channels in anandamide‐induced mesenteric vasorelaxation in isolated rat cirrhotic vessels.

Long-term cannabinoid type 2 receptor agonist therapy decreases bacterial translocation in rats with cirrhosis and ascites.

BACKGROUND & AIMS Intestinal hyperpermeability, impaired peritoneal macrophages (PMs) phagocytosis, and bacterial translocation (BT), resulting in increased systemic and local infection/inflammation such as spontaneous bacterial peritonitis (SBP) together with increased tumor necrosis factor-α (TNFα) levels, are all implicated in the pathogenesis of cirrhosis-related complications. Manipulation of the cannabinoid receptors (CB1R and CB2R), which are expressed on the gut mucosa and PMs, has been reported to modulate intestinal inflammation and systemic inflammatory cytokine release. Our study aims to explore the effects of chronic CB1R/CB2R agonist/antagonist treatments on relevant abnormalities in cirrhotic ascitic rats. METHODS Vehicle, archidonyl-2-chloroethylamide (ACEA, CB1R agonist), JWH133 (CB2R agonist), and AM630 (CB2R antagonist) were given to thioacetamide (TAA) and common bile duct ligation (BDL) cirrhotic rats with ascites for two weeks and various measurement were performed. RESULTS Compared to sham rats, CB2Rs were downregulated in cirrhotic rat intestines and PMs. The two-week JWH133 treatment significantly decreased systemic/intestinal oxidative stress, TNFα and inflammatory mediators, infection, intestinal mucosal damage and hyperpermeability; the JWH133 treatment also decreased bacterial overgrowth/adhesion, BT and SBP, upregulated intestinal tight junctions and downregulated the PM TNFα receptor/NFκBp65 protein expression in cirrhotic rats. Acute and chronic JWH133 treatment corrected the TNFα-induced suppression of phagocytosis of cirrhotic rat PMs, which then could be reversed by concomitant AM630 treatment. CONCLUSIONS Our study suggests that CB2R agonists have the potential to treat BT and various relevant abnormalities through inhibition of systemic/intestinal oxidative stress, inflammatory cytokines and TNFα release in cirrhosis. Overall, the chronic CB2R agonist treatment affects multiple approach mechanisms, and its direct effect on the hyperdynamic circulation is only minor.

Hypertension is an important predictor of recurrent colorectal adenoma after screening colonoscopy with adenoma polypectomy

Background: The predictors of recurrent colorectal adenoma have not been fully examined. This study aimed to evaluate the predictors of recurrent colorectal adenoma after initial screening colonoscopy with adenoma polypectomy. Methods: A retrospective cohort study was conducted at the Taipei Veterans General Hospital from 2003 to 2011. After screening, 356 patients who had undergone two consecutive colonoscopies with colorectal adenoma polypectomy at the initial colonoscopy were enrolled. The recurrence group was patients with recurrent colorectal adenoma at the second colonoscopy, whereas the nonrecurrence group was patients without recurrence. Anthropometric data, biochemical tests, metabolic comorbidities, and adenoma characteristics at initial colonoscopy were compared between the two groups. Cox proportional hazard regression analysis was conducted to identify the predictors of recurrent colorectal adenoma. Results: During a mean follow‐up interval of 3.07 ± 1.42 years, 94 patients (26.4%) were in the recurrence group, 262 patients (73.6%) were in the nonrecurrence group. The recurrence group was older, had a wider waist circumference, higher levels of serum alanine aminotransferase (ALT) and triglyceride, a higher prevalence of smoking, nonalcoholic fatty liver disease, metabolic syndrome, and hypertension, and a higher occurrence of initial multiply‐located adenomas when compared with the nonrecurrence group (p < 0.05). Cox regression analysis showed that hypertension, smoking, higher ALT level (>40 IU/mL), and multiply‐located adenomas were independent predictors for recurrent colorectal adenoma. The risk of recurrent adenoma increased when hypertension was combined with smoking, high ALT level, or multiply‐located adenomas. Conclusion: Hypertension is an important predictor for recurrent colorectal adenoma after screening colonoscopy with polypectomy.

Hemodynamic effects of one week of carvedilol administration on cirrhotic rats

BackgroundCarvedilol is a nonselective β-blocker with α1-adrenergic blocking activity. It has been shown to decrease portal pressure in cirrhotic patients. The current study was undertaken to evaluate the possible mechanism of carvedilol on hemodynamics in cirrhotic rats with portal hypertension produced by common bile duct ligation.MethodsMale Sprague-Dawley rats received either a sham operation or common bile duct ligation. Three weeks after surgery, both sham-operated and cirrhotic rats were randomly assigned to receive vehicle or carvedilol 5 mg · kg−1 · 12 h−1 by gastric gavage for 1 week. Hemodynamic measurements, serum biochemistry, serum nitrate/nitrite and 6-keto-PGF1α levels, and aortic mRNA expression of eNOS and COX-1 were performed on the eighth day after drug administration.ResultsCarvedilol treatment did not affect serum biochemistry in either sham-operated or cirrhotic rats. In sham-operated rats, administration of carvedilol significantly decreased the heart rate without affecting other hemodynamic values. In contrast, in cirrhotic rats, administration of carvedilol significantly decreased the cardiac index, portal pressure, heart rate, and portal territory blood flow, and it significantly increased systemic and portal territory vascular resistances. The hepatocollateral resistance was significantly decreased, but the hepatic arterial blood showed no significant changes. In sham-operated rats treated with carvedilol, serum nitrate/nitrite and 6-keto-PGF1α levels were not affected. In contrast, cirrhotic rats receiving carvedilol showed a significant decrease in serum nitrate/nitrite and 6-keto-PGF1α levels, associated with a decrease in aortic mRNA expression of eNOS and COX-1 compared with those receiving vehicle.ConclusionsCarvedilol decreased portal pressure through a reduction of splanchnic blood flow associated with a decrease in hepatocollateral resistance. Additionally, administration of carvedilol decreased endothelial-related vasodilatory activities.