The Effect of the First Spontaneous Bacterial Peritonitis Event on the Mortality of Cirrhotic Patients with Ascites: A Nationwide Population-Based Study in Taiwan

BACKGROUND/AIMS: Spontaneous bacterial peritonitis (SBP) contributes to poorer short-term mortality in cirrhotic patients with ascites. However, it is unknown how long the effect of the first SBP event persists in these patients. METHODS: The National Health Insurance Database, derived from the Taiwan National Health Insurance Program, was used to identify and enroll 7,892 cirrhotic patients with ascites who were hospitalized between January 1 and December 31, 2007. All patients were free from episodes of SBP from 1996 to 2006. RESULTS: The study included 1,176 patients with SBP. The overall 30-day, 90-day, 1-year, and 3-year mortality rates in this group were 21.8%, 38.9%, 57.5%, and 73.4%, respectively. The overall 30-day, 90-day, 1-year, and 3-year mortality rates in the non-SBP group were 15.7%, 32.5%, 53.3%, and 72.5%, respectively. After adjusting for gender, age, and other medical comorbidities, the adjusted hazard ratios of SBP for 30-day, 30- to 90-day, 90-day to 1-year, and 1- to 3-year mortality were 1.49 (95% confidence interval [CI], 1.30 to 1.71), 1.19 (95% CI, 1.02 to 1.38), 1.04 (95% CI, 0.90 to 1.20), and 0.90 (95% CI, 0.77 to 1.05), respectively, compared with the non-SBP group. CONCLUSIONS: The effect of SBP on the mortality of cirrhotic patients with ascites disappeared in those surviving more than 90 days after the first SBP event.

A fourfold increase of oesophageal variceal bleeding in cirrhotic patients with a history of oesophageal variceal bleeding

<p><b>INTRODUCTION</b>Large, recent population-based data for evaluating the predictors of oesophageal variceal bleeding (OVB) among cirrhotic patients is still lacking. This study aimed to determine the cumulative incidence of OVB among cirrhotic patients and identify the predictors of OVB occurrence.</p><p><b>METHODS</b>Patient information on 38,172 cirrhotic patients without a history of OVB, who were discharged between 1 January 2007 and 31 December 2007, was obtained from the Taiwan National Health Insurance Database for this study. All patients were followed up for three years. Death was the competing risk when calculating the cumulative incidences and hazard ratios (HRs) of OVB.</p><p><b>RESULTS</b>OVB was present in 2,609 patients (OVB group) and absent in 35,563 patients (non-OVB group) at hospitalisation. During the three-year follow-up period, the cumulative incidence of OVB was 44.5% and 11.3% in the OVB and non-OVB group, respectively (p < 0.001). Modified Cox regression analysis showed that the HR of OVB history was 4.42 for OVB occurrence (95% confidence interval [CI] 4.13-4.74). Other predictors for OVB occurrence included hepatocellular carcinoma (HR 1.16, 95% CI 1.09-1.24), young age (HR 0.98, 95% CI 0.98-0.98), ascites (HR 1.46, 95% CI 1.37-1.56), alcohol-related disorders (HR 1.20, 95% CI 1.12-1.28), peptic ulcer bleeding (HR 1.26, 95% CI 1.13-1.41) and diabetes mellitus (HR 1.14, 95% CI 1.06-1.23).</p><p><b>CONCLUSION</b>Cirrhotic patients have a fourfold increased risk of future OVB following the first incidence of OVB.</p>

Sedanolide induces autophagy through the PI3K, p53 and NF-κB signaling pathways in human liver cancer cells.

Sedanolide (SN), a phthalide-like compound from celery seed oil, possesses antioxidant effects. However, the effect of SN on cell death in human liver cancer cells has yet to be determined. In this study, cell viability determination, monodansylcadaverine (MDC) fluorescent staining and immunoblot analysis were performed to determine autophagy induction and autophagy-induced protein expression changes via molecular examination after human liver cancer (J5) cells were treated with SN. Our studies demonstrate that SN suppressed J5 cell viability by inducing autophagy. Phosphoinositide 3-kinase (PI3K)-I, mammalian target of rapamycin (mTOR) and Akt protein levels decreased, whereas PI3K-III, LC3-II and Beclin-1 protein levels increased following SN treatment in J5 cells. In addition, SN treatment upregulated nuclear p53 and damage-regulated autophagy modulator (DRAM) and downregulated cytosolic p53 and Tp53-induced glycolysis and apoptosis regulator (TIGAR) expression in J5 cells. Furthermore, the cytosolic phosphorylation of inhibitor of kappa B (IκB) and nuclear p65 and the DNA-binding activity of NF-κB increased after SN treatment. These results suggest that SN induces J5 cell autophagy by regulating PI3K, p53 and NF-κB autophagy-associated signaling pathways in J5 cells.

Induction of α-phellandrene on autophagy in human liver tumor cells.

α-Phellandrene (α-PA) is a cyclic monoterpene. To investigate the induction of autophagy by α-PA and its mechanism, human liver tumor cells (J5) were incubated with α-PA and analyzed for cell viability and the molecular regulation of pre-autophagosome origination and autophagosome formation. According to the results, PI3K-I, mTOR, and Akt protein levels were decreased after α-PA treatment compared to those of the control group (p < 0.05). The phosphorylation of Bcl-2, and PI3K-III, LC3-II and Beclin-1 protein levels in J5 cells were increased after α-PA treatment (p < 0.05). In addition, α-PA up-regulated nuclear p53 and down-regulated cytoplasmic p53 expression in J5 cells. The NF-κB pathway was activated, as indicated by increase in cytosolic phosphorylated IκB, nuclear NF-κB levels, and the DNA-binding activity of NF-κB after α-PA treatment in J5 cells (p < 0.05). These results suggest that α-PA can induce J5 cell autophagy by regulating mTOR and LC-3II expression, p53 signaling, and NF-κB activation in J5 cells.

The effect of bacterial infections in cirrhotic patients with esophageal variceal bleeding.

BACKGROUND: Cirrhotic patients are prone to having bacterial infections due to impaired innate immunity. This nationwide population-based study aimed to identify the effect of bacterial infections on the mortality of the cirrhotic patients with esophageal variceal bleeding (EVB). MATERIAL AND METHODS: The Taiwan National Health Insurance Database was used to collect data about the cirrhotic patients receiving endoscopic procedures for EVB between January 1, 2004 and December 31, 2004. The enrolled patients were followed up individually for one year to identify their 6-week and 1-year mortalities. RESULTS: Of the 2,053 cirrhotic patients with EVB, 318 (15.5 %) were diagnosed with bacterial infections. Compared to non-infection group, the adjusted hazard rations (HRs) of bacterial infection for 6-week and 1-year mortalities were 2.69 (2.06-3.52) and 1.89 (1.56-2.28), respectively. Compared to non-infection group, the HRs of pneumonia, spontaneous bacterial peritonitis, urinary tract infection, and sepsis without specific focus (SWSF) were 3.54, 1.91, 1.04, and 3.95 for 6-week mortality, and 3.18, 1.52, 1.15, and 2.23 for 1-year mortality of cirrhotic patients with EVB. CONCLUSIONS: In cirrhotic patients with EVB, bacterial infections increase 2.7 folds of 6-week mortality and 1.9 folds of 1-year mortality. Of all infections, pneumonia and SWSF contributed higher risks for mortality.

Liver cirrhosis as a real risk factor for necrotising fasciitis: a three-year population-based follow-up study

<p><b>INTRODUCTION</b>Necrotising fasciitis (NF) is often found in patients with diabetes mellitus, chronic renal failure, alcoholism, malignancy or liver cirrhosis. However, it remains unknown whether liver cirrhosis is an independent risk factor for the occurrence of NF. This study aimed to determine whether liver cirrhosis is an independent risk factor for the occurrence of NF, and to identify the relationship between severity of liver cirrhosis and occurrence of NF.</p><p><b>METHODS</b>The National Health Insurance Research Database, maintained by Taiwan's National Health Insurance programme, was retrospectively analysed, and the hospitalisation data of 40,802 cirrhotic patients and 40,865 randomly selected, age‑ and gender‑matched non‑cirrhotic control patients was collected. The medical records of all patients were individually followed for a three‑year period from the patients' first hospitalisation in 2004.</p><p><b>RESULTS</b>During the three‑year follow‑up period, there were 299 (0.7%) cirrhotic patients with NF and 160 (0.4%) non‑cirrhotic patients with NF. Cox regression analysis showed that liver cirrhosis was a risk factor for the occurrence of NF during the study period (hazard ratio 1.982; p < 0.001). Among cirrhotic patients, those with complicated liver cirrhosis had a higher risk for the occurrence of NF than patients with non‑complicated liver cirrhosis (hazard ratio 1.320; p = 0.028).</p><p><b>CONCLUSION</b>Cirrhotic patients had a higher risk for the occurrence of NF than non‑cirrhotic patients, and the risk for NF was especially high among patients with complicated liver cirrhosis.</p>

Differential blood lipid-lowering effects of alkylsulfonated chitosan of different molecular weights in Syrian hamsters in vivo.

This study investigated the effects of alkylsulfonated chitosan of different molecular weights on intestinal lipid absorption, blood lipid profiles and circulating adhesion molecules. Syrian hamsters were fed an AIN-93G-based high­fat diet (HFD) and were orally administered 5 or 10 mg/kg BW of oligomer (6 kDa) chitosan (OC), low­molecular-weight (70 kDa) chitosan (LMC) or high­molecular-weight (200 kDa) chitosan (HMC) four times per week for 12 weeks. Animals receiving 2.5 mg/kg BW lovastatin (LOVA) served as a positive control. The blood lipid profiles of these control animals revealed that all chitosans and LOVA significantly decreased total triglyceride, total cholesterol, low­density lipoprotein (LDL)-cholesterol and very­low­density lipoprotein (VLDL)-cholesterol levels in a dose­dependent manner compared to the HFD-fed controls (P<0.05). The blood lipid lowering effectiveness of the three chitosans followed the order of LMC>OC>HMC. Hamsters receiving 5 and 10 mg/kg LMC (P<0.05) exhibited an increase in fecal fat content. Immunoblot assay revealed that acyl­coenzyme A:cholesterol acyltransferase-2 (ACAT-2) expression was suppressed in all chitosan-fed animals compared to the HFD-fed controls (P<0.05). These results suggest that chitosan effectively decreases blood lipid content, and its effectiveness depends on the molecular size of chitosan. The hypolipidemic effect of chitosan is partly attributed to its suppression of intestinal lipid absorption and hepatic ACAT-2 expression.

The Risk of Cellulitis in Cirrhotic Patients: A Nationwide Population-Based Study in Taiwan

BACKGROUND/AIMS: Cellulitis is a common infectious disease. However, the risk of cellulitis in cirrhotic patients is not well established, and whether liver cirrhosis is a risk factor for cellulitis remains unknown. This study evaluated the relationship between cellulitis and liver cirrhosis. METHODS: The National Health Insurance Database, which was derived from the Taiwan National Health Insurance program, was used to identify patients. The study group consisted of 39,966 patients with liver cirrhosis, and the comparison group consisted of 39,701 randomly selected age- and sex-matched patients. RESULTS: During the 3-year follow-up period, 2,674 (6.7%) patients with liver cirrhosis developed cellulitis, and 1,587 (4.0%) patients without liver cirrhosis developed cellulitis (p<0.001). Following a Cox's regression analysis adjusted for age, sex, and underlying medical disorders, the cirrhotic patients demonstrated a greater risk for the occurrence of cellulitis than the non-cirrhotic patients during the 3-year period (hazard ratio [HR], 1.66; 95% confidence interval [CI], 1.55 to 1.77; p<0.001). Additionally, cirrhotic patients with complications also had a greater risk for the occurrence of cellulitis than those patients without complications (HR, 1.23; 95% CI, 1.14 to 1.33; p<0.001). CONCLUSIONS: We conclude that cirrhotic patients have a greater risk of cellulitis than non-cirrhotic patients.

Different Clinical Characteristics Among Aeromonas hydrophila, Aeromonas veronii biovar sobria and Aeromonas caviae Monomicrobial Bacteremia

This study aimed to compare the clinical presentations of Aeromonas hydrophila, A. veronii biovar sobria and A. caviae monomicrobial bacteremia by a retrospective method at three hospitals in Taiwan during an 8-yr period. There were 87 patients with A. hydrophila bacteremia, 45 with A. veronii biovar sobria bacteremia and 22 with A. caviae bacteremia. Compared with A. hydrophila and A. veronii biovar sobria bacteremia, A. caviae bacteremia was more healthcare-associated (45 vs 30 and 16%; P = 0.031). The patients with A. caviae bacteremias were less likely to have liver cirrhosis (27 vs 62 and 64%; P = 0.007) and severe complications such as shock (9 vs 40 and 47%; P = 0.009) and thrombocytopenia (45 vs 67 and 87%; P = 0.002). The APACHE II score was the most important risk factor of Aeromonas bacteremia-associated mortalities. The APACHE II scores of A. caviae bacteremias were lower than A. hydrophila bacteremia and A. veronii biovar sobria bacteremia (7 vs 14 and 16 points; P = 0.002). In conclusion, the clinical presentation of A. caviae bacteremia was much different from A. hydrophila and A. veronii biovar sobria bacteremia. The severity and mortality of A. caviae bacteremia were lower than A. hydrophila or A. veronii biovar sobria bacteremia.

Diallyl sulfide inhibits murine WEHI-3 leukemia cells in BALB/c mice in vitro and in vivo.

It is well documented that enhanced garlic (Allium sativum) consumption leads to decrease in the cancer incidences. Diallyl sulfide (DAS), one of the components of garlic, induces cytotoxicity and apoptosis in many cancer cell lines. The present studies are focused on the in vivo effects of DAS on leukemia WEHI-3 cells in the BALB/c mice. We examined the effects of DAS on the cytotoxicity of WEHI-3 cells and results indicated that DAS decreased the percentage of viable WEHI-3 cells and these effects are dose-dependent. We examined the effects of DAS on WEHI-3 in vivo and the results indicated that DAS decreased the percentage of Mac-3 and CD11b, indicating that the differentiation of the precursor of macrophage cells was inhibited. DAS stimulated the percentage of CD3 and CD19, indicating that the differentiation of the precursor of T and B cells promoted. The weights of liver and spleen indicated that DAS decreased the weight of these organs after being compared to the control groups. One of the major characteristic of WEHI-3 leukemia is the enlarged spleen in murine after intraperitoneal (i.p.) injection of WEHI-3 cells. In conclusion, DAS affects WEHI-3 cells both in vitro and in vivo.

Capsaicin-induced apoptosis in human hepatoma HepG2 cells.

Capsaicin, a pungent ingredient of red pepper, has been reported to possess antitumor activities. In this study, the effects of capsaicin on human HepG2 cells were investigated. Capsaicin reduced viability by PI incorporation in HepG2 cells in a dose and time dependent manner. Capsaicin promoted intracellular Ca2+ production and reactive oxygen species (ROS). The alpha psi(m) significantly decreased after capsaicin treatment for 24 h. Co-treatment of HepG2 cells with capsaicin and BAPTA (an intracellular Ca2+ chelator) significantly reduced intracellular Ca2+ levels, prevented alpha psi(m) disruption and inhibited apoptosis induction. The protein levels of Bcl-2 decreased and Bax increased in the mitochondrial fraction while the Bax protein decreased, and p53 and cytochrome c protein levels increased in the cytosolic fraction in HepG2 cells after capsaicin treatment for 24 h by Western blot. Immunostaining and confocal microscopic analysis also showed that capsaicin promoted cytoplasmic GADD153 expression and GRP78 nuclear translocation. The caspase-3 activity significantly increased after capsaicin treatment for 24 h. Our results indicated that the capsaicin-induced apoptosis in HepG2 cells may result from the elevation of intracellular Ca2+ production, ROS, disruption of alpha psi(m), regulation of Bcl-2 family protein expression and caspase-3 activity.

Nosocomial acinetobacter genomic species 13 TU endocarditis following an endoscopic procedure.

We report a rare case of prosthetic valve endocarditis caused by Acinetobacter genomic species 13 TU. This patient had rheumatic heart disease and received prosthetic mitral valve replacement eleven years previously. He was admitted due to tarry stool. Endoscopic procedure showed two gastric ulcers and some mucous breaks at the distal esophagus. He had a fever on the eleventh hospital day. Persistent Acinetobacter bacteremia was noted with conjunctiva hemorrhage. The pathogen was identified as Acinetobacter genomic species 13 TU by PCR-based method. According to his whole course of disease, the most possible portal of entry was via the endoscopic procedure.