Anticoagulation therapy early is safe in portal vein thrombosis patients with acute variceal bleeding: a multi-centric randomized controlled trial.

Portal vein thrombosis (PVT) and acute variceal bleeding (AVB) are frequent complications of cirrhosis. The efficacy, safety, and timing of anticoagulant treatment in cirrhotic patients with PVT and AVB are contentious issues. We aimed to establish the safety and efficacy of initiating nadroparin calcium-warfarin sequential (NWS) anticoagulation therapy early after esophageal variceal band ligation within PVT patients having cirrhosis and AVB. Cirrhotic patients having AVB and PVT who underwent EVL were included and randomly allocated to either the NWS therapy group (1-month nadroparin calcium by subcutaneous injection following 5-month warfarin through oral administration, n = 43) or the control group (without any anticoagulation therapy, n = 43). The primary endpoint was the rate of PVT recanalization. Secondary endpoints included major bleeding events mainly referring to variceal rebleeding (5-day failure, 14-day, 4-week, 6-week, and 6-month rebleeding rates) and mortality after EVL. The overall recanalization (complete and partial) rate in the NWS therapy group was significantly higher than that in the control group (67.4% vs. 39.5%, P = 0.009). Low Child-Pugh score (P = 0.039, OR: 0.692, 95% CI 0.488-0.982), D-dimer < 2.00 ug/mL (P = 0.030, OR: 3.600, 95% CI 1.134-11.430), and NWS anticoagulation therapy (P = 0.002, OR: 4.189, 95% CI 1.660-10.568) were the predictors of PVT recanalization through univariate analysis of binary logistic regression. NWS anticoagulation therapy (P = 0.003, OR: 4.506, 95% CI 1.687-12.037) was the independent factor of recanalization through multivariate analysis. Nobody bled except for variceal rebleeding. Five-day failure and 14-day rebleeding were zero. There were no significantly different in 4-week (2.3% vs. 4.7%, P = 1.000), 6-week (4.7% vs. 9.3%, P = 0.672) and 6-month rebleeding (18.6% vs. 20.9%, P = 0.787) between the two groups. There was no mortality during six months follow-up. Low serum albumin (P = 0.011, OR: 0.844, 95% CI 0.741-0.962), high MELD score (P = 0.003, OR: 1.564, 95% CI 1.167-2.097) and Child-Pugh score (P = 0.006, OR: 1.950, 95% CI 1.206-3.155) were predictors of rebleeding by univariate analysis of binary logistic regression analysis. The Child-Pugh score (7 [6-8] vs. 6 [5-7], P = 0.003) and albumin levels (33.93 ± 5.30 vs. 37.28 ± 4.32, P = 0.002) were improved in the NWS therapy group at six months. In PVT patients with cirrhosis and AVB, starting NWS anticoagulation therapy early after EVL was safe and effective. It has the potential to raise albumin levels and improve liver function.

Portal vein thrombosis associated with high 14-day and 6-week rebleeding in patients after oesophageal variceal band ligation: a retrospective, multicentre, nested case-control study.

BACKGROUND AND AIMS: The association between prognosis of variceal bleeding and portal vein thrombosis (PVT) is unclear. In this multicentre study, we determined the effect of PVT on rebleeding and mortality in patients with acute variceal bleeding (AVB) after oesophageal variceal band ligation (EVL). METHODS: Cirrhotic patients with AVB who had undergone EVL were included. The patients were allocated to either the PVT group or the control cirrhotic group (CCG) based on the presence or absence of PVT. One-year rebleeding episodes and mortality after EVL were recorded. RESULTS: A total of 218 cirrhotic patients with AVB from 3 centres were included. Patients with PVT had a higher rate of 14-day and 6-week rebleeding than those without PVT (14-day: 8.26% vs. 1.83%, p = 0.03; 6-week: 11.92% vs. 1.83%, p = 0.003). The rates of 5-day failure (3.67% vs. 0.92%, p = 0.175), 1-year rebleeding (21.10% vs. 20.18%, p = 0.867), and 14-day, 6-week, and 1-year mortality were similar between the groups (14-day: 3.67% vs. 0.92%, p = 0.175; 6-week: 3.67% vs. 0.92%, p = 0.175; 1-year: 3.67% vs. 1.83%, p = 0.408). The Child-Pugh class [p = 0.022, hazard ratio (HR): 1.453; 95% confidence interval (CI) 1.056-1.998], PVT (p = 0.050, HR: 4.622, 95% CI 0.999-21.395), albumin < 30 g/L (p = 0.023, HR: 5.886, 95% CI 1.272-27.245), and number of bands (p = 0.010, HR: 1.207, 95% CI 1.046-1.393) were identified as the predictors for 14-day rebleeding; the multivariate analysis revealed only the number of bands (p = 0.009, HR: 1.247, 95% CI 1.056-1.473) as the independent factor. PVT (p = 0.012, HR: 6.732, 95% CI 1.519-29.835) and albumin < 30 g/L (p = 0.027, HR: 3.643, 95% CI 1.160-11.441) were identified as predictors for 6-week rebleeding; however, only PVT (p = 0.015, HR: 6.380, 95% CI 1.427-28.515) was found to be the independent factor in the multivariate analysis. Further analysis showed that superior mesenteric vein (SMV) thrombosis is the only risk factor predicting 6-week rebleeding in patients with PVT (p = 0.032, HR: 3.405, 95% CI 1.112-10.429). CONCLUSIONS: PVT was associated with high 14-day and 6-week rebleeding in patients after EVL. SMV thrombosis was the only risk factor for 6-week rebleeding in patients with PVT. High albumin levels may serve as a protective factor for the 14-day and 6-week rebleeding risk. PVT was not responsible for mortality after EVL during 1-year follow-up.

The neurovascular protective effects of huperzine A on D-galactose-induced inflammatory damage in the rat hippocampus.

BACKGROUND: Chronic administration of D-galactose (D-gal) results in oxidative stress and chronic inflammatory aging. Age-related changes in the brain result in neurovascular damage and blood-brain barrier (BBB) dysfunction. However, little is known regarding D-gal-induced neurovascular damage, as well as the protective effects of huperzine A. OBJECTIVE: The purpose of this study was to utilize a D-gal-induced rat model to investigate the activation of neurovascular inflammatory damage and apoptosis in the rat hippocampus and to understand whether huperzine A alleviates D-gal-induced neuronal and vascular inflammatory injury. METHODS: Aging rats were treated with D-gal (300 mg/kg s.c. for 8 weeks), were coadministered D-gal and huperzine A (D-gal 300 mg/kg and huperzine A 0.1 mg/kg s.c. for 8 weeks) or served as the saline-treated control group rats (same volume of saline given subcutaneously for 8 weeks). Changes in hippocampal morphology and biomarkers of inflammatory damage were analyzed. RESULTS: Our study revealed that chronic administration of D-gal resulted in the activation of glia and vascular endothelial cells and upregulation of mRNA and protein levels of cell-associated adhesion molecules and inflammatory cytokines via nuclear factor (NF)-κB inhibitor degradation and NF-κB nuclear translocation. The inflammatory injury caused significant BBB dysfunction, decreased density of tight junctions (TJs) and apoptosis in the rat hippocampus. Coadministration of huperzine A not only markedly inhibited the D-gal-induced increase in acetylcholinesterase (AChE) activity, but also alleviated D-gal-induced neurovascular damage by inhibiting D-gal-induced NF-κB activation, improving cerebrovascular function and suppressing the D-gal-induced decrease in the density and protein levels of TJs and cell apoptosis. CONCLUSIONS: Our findings provided evidence that D-gal induced a proinflammatory phenotype mediated by NF-κB in the rat hippocampus. Moreover, huperzine A suppressed D-gal-induced neurovascular damage and BBB dysfunction, partly by preventing NF-κB nuclear translocation. The inhibiting effect of huperzine A on AChE activity might play an important role in attenuating D-gal-induced inflammatory damage.

The anti-inflamm-aging and hepatoprotective effects of huperzine A in D-galactose-treated rats.

Oxidative stress contributes to a chronic inflammatory process referred to as "inflamm-aging". Acetylcholinesterase inhibitors (AChEI) can enhance cholinergic transmission and act as anti-inflammatory agents via immunocompetent cells expressing α-7 acetylcholine receptors (AChR). The present study explores the possible role of huperzine A, a reversible and selective AChEI, against D-gal-induced oxidative damage, cell toxicity and inflamm-aging in rat livers. In two-month-old rats with normal liver function, an 8-week administration of D-gal (300 mg/kg subcutaneously (s.c.) injected), significantly increased hepatic impairment, ROS generation and oxidative damage, hepatic senescence, nuclear factor-kappa B (NF-κB) activation and inflammatory responses. An 8-week co-administration of both D-gal (300 mg/kg s.c.) and huperzine A (0.1 mg/kg s.c.) not only significantly decreased hepatic function impairment, ROS generation, oxidative damage, but also suppressed inflamm-aging by inhibiting hepatic replicative senescence, AChE activity, IκBα degradation, NF-κB p65 nuclear translocation and inflammatory responses. The expression levels of pro-inflammatory cytokine mRNA and proteins, such as TNFα, IL-1ß and IL-6 decrease significantly, and the protein levels of the anti-inflammatory cytokine IL-10 display an obvious increase. These findings indicated that D-gal-induced hepatic injury and inflamm-aging in the rat liver was associated with the development of a pro-inflammatory phenotype in this organ. D-gal induced damage-associated molecular patterns (DAMPs) because oxidative damages might play an important role in D-gal-induced hepatic sterile inflammation. Huperzine A exhibited protective effects against D-gal-induced hepatotoxicity and inflamm-aging by inhibiting AChE activity and via the activation of the cholinergic anti-inflammatory pathway. The huperzine A mechanism might be involved in the inhibition of DAMPs-mediated NF-κB nuclear localization and activation.

Prevalence and factors associated with nonalcoholic fatty liver disease in Shanghai work-units.

BACKGROUNDS: Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in Asians. However, data on prevalence and factors associated with NAFLD in Asians are lacking. The aim of this study is to investigate the prevalence of NAFLD in Shanghai employees to assess the relationship between NAFLD and age, gender, metabolic risk factors in this studied population. METHODS: We selected 7152 employees of Shanghai work-units. Each of them underwent detailed medical history-taking, physical examination, laboratory assessments and abdominal ultrasonography. The diagnosis of NAFLD was done according to established criteria. Receiver operating characteristics (ROC) curves were applied to detect areas under the ROC curves for each index. Nominal logistic regression analysis was used to estimate the odds ratio for risk factors of NAFLD. RESULTS: About 38.17% employees had NAFLD, more in men than in women. The prevalence of NAFLD increased with increasing age. In both genders, the prevalence of metabolic factors was higher in the NAFLD group. Body max index, waist circumference, weight-to-height ratio, blood pressure, blood glucose, total cholesterol, triglyceride, low density lipoprotein, high density lipoprotein and uric acid were found to have a diagnostic value for NAFLD. Body max index is a better index for diagnosing NAFLD. Uric acid is a new diagnosing index not inferior to lipid metabolic factors. Metabolic factors can increase the risk of NAFLD up to 1.5 ~ 3.8 times. CONCLUSIONS: Older age, male gender, metabolic factors such as obesity, abdominal obesity, dyslipidemia, hypertension or type 2 diabetes are risk factors for NAFLD. Prevalence of NAFLD in Shanghai employees is high. Prevention is extremely important. Those achieve the critical point should have early intervention.