Ming-Chih Hou

Antibiotic prophylaxis after endoscopic therapy prevents rebleeding in acute variceal hemorrhage: A randomized trial

Bacterial infection may adversely affect the hemostasis of patients with gastroesophageal variceal bleeding (GEVB). Antibiotic prophylaxis can prevent bacterial infection in such patients, but its role in preventing rebleeding is unclear. Over a 25‐month period, patients with acute GEVB but without evidence of bacterial infection were randomized to receive prophylactic antibiotics (ofloxacin 200 mg i.v. q12h for 2 days followed by oral ofloxacin 200 mg q12h for 5 days) or receive antibiotics only when infection became evident (on‐demand group). Endoscopic therapy for the GEVB was performed immediately after infection work‐up and randomization. Fifty‐nine patients in the prophylactic group and 61 patients in the on‐demand group were analyzed. Clinical and endoscopic characteristics of the gastroesophageal varices, time to endoscopic treatment, and period of follow‐up were not different between the two groups. Antibiotic prophylaxis decreased infections (2/59 vs. 16/61; P < .002). The actuarial probability of rebleeding was higher in patients without prophylactic antibiotics (P = .0029). The difference of rebleeding was mostly due to early rebleeding within 7 days (4/12 vs. 21/27, P = .0221). The relative hazard of rebleeding within 7 days was 5.078 (95% CI: 1.854–13.908, P < .0001). The multivariate Cox regression indicated bacterial infection (relative hazard: 3.85, 95% CI: 1.85–13.90) and association with hepatocellular carcinoma (relative hazard: 2.46, 95% CI: 1.30–4.63) as independent factors predictive of rebleeding. Blood transfusion for rebleeding was also reduced in the prophylactic group (1.40 ± 0.89 vs. 2.81 ± 2.29 units, P < .05). There was no difference in survival between the two groups. In conclusion, antibiotic prophylaxis can prevent infection and rebleeding as well as decrease the amount of blood transfused for patients with acute GEVB following endoscopic treatment. (HEPATOLOGY 2004;39:746–753.)

A randomized trial of endoscopic treatment of acute gastric variceal hemorrhage: N‐Butyl‐2‐Cyanoacrylate injection versus band ligation

Progression of gastric variceal hemorrhage (GVH) is poorer than esophageal variceal bleeding. However, data on its optimal treatment are limited. We designed a prospective study to compare the efficacy of endoscopic band ligation (GVL) and endoscopic N‐butyl‐2‐cyanoacrylate injection (GVO). Liver patients with cirrhosis with or without concomitant hepatocellular carcinoma (HCC) and patients presenting with acute GVH were randomized into two treatment groups. Forty‐eight patients received GVL, and another 49 patients received GVO. Both treatments were equally successful in controlling active bleeding (14/15 vs. 14/15, P = 1.000). More of the patients who underwent GVL had GV rebleeding (GVL vs. GVO, 21/48 vs. 11/49; P = .044). The 2‐year and 3‐year cumulative rate of GV rebleeding were 63.1% and 72.3% for GVL, and 26.8% for both periods with GVO; P = .0143, log‐rank test. The rebleeding risk of GVL was sustained throughout the entire follow‐up period. Multivariate Cox regression indicated that concomitance with HCC (relative hazard: 2.453, 95% CI: 1.036‐5.806, P = .041) and the treatment method (GVL vs. GVO, relative hazard: 2.660, 95% CI: 1.167‐6.061, P = .020) were independent factors predictive of GV rebleeding. There was no difference in survival between the two groups. Severe complications attributable to these two treatments were rare. In conclusion, the efficacy of GVL to control active GVH appears not different to GVO, but GVO is associated with a lower GV rebleeding rate. (HEPATOLOGY 2006;43:690–697.)

The effect of ciprofloxacin in the prevention of bacterial infection in patients with cirrhosis after upper gastrointestinal bleeding

Objectives:Cirrhotic patients with upper gastrointestinal bleeding are prone to bacterial infection. The aim of this study was to investigate the efficacy of prophylactic intestinal decontamination with oral ciprofloxacin for the prevention of bacterial infections in cirrhotic patients with upper gastrointestinal bleeding.Methods:A total of 120 cirrhotic patients with acute upper gastrointestinal bleeding were enrolled. Sixty patients received ciprofloxacin 500 mg twice daily given orally or through nasogastric tube immediately after upper gastrointestinal endoscopic examination; drug administration continued for 7 days. The remaining 60 patients, who received placebo, served as controls.Results:The incidence of proven bacterial infection in the ciprofloxacin-treated group was significantly lower than that of placebo group (10%vs 45%, p < 0.001). The incidences of bacteremia, spontaneous bacterial peritonitis, and urinary tract infection in the ciprofloxacin-treated group were significantly lower than those in the placebo group (0%vs 23%, 3.3%vs 13%, and 5%vs 18%, respectively; p < 0.05, respectively). Multivariate logistic regression analysis showed that a lack of prophylactic treatment with ciprofloxacin and severity of cirrhosis were the independent significant predictors for cirrhotic patients with acute gastrointestinal bleeding with infection.Conclusions:Prophylactic intestinal decontamination with oral ciprofloxacin is effective in the prevention of bacterial infections in patients with cirrhosis who were suffering from acute upper gastrointestinal hemorrhage.

Plasma Interleukin-6 Levels in Patients with Cirrhosis Relationship to Endotoxemia, Tumor Necrosis Factor-α, and Hyperdynamic Circulation

BACKGROUND Liver cirrhosis with portal hypertension is associated with hyperdynamic circulation characterized by generalized vasodilatation and increased cardiac output and regional blood flows. Patients with liver cirrhosis present with increased levels of interleukin-6 (IL-6), which may inhibit vascular smooth-muscle contraction. We investigated whether increased plasma IL-6 levels contribute to the pathogenesis of hyperdynamic circulation observed in cirrhotic patients and whether they are correlated with plasma tumor necrosis factor-alpha (TNF-alpha) and endotoxin concentrations. METHODS In 58 consecutive cirrhotic patients and 34 healthy subjects the plasma concentrations of TNF-alpha and IL-6 were measured with enzyme-linked immunosorbent assay, and endotoxin determinations with a limulus assay. In addition, 52 cirrhotic patients underwent a hemodynamic study using Swan-Ganz catheterization. RESULTS Plasma TNF-alpha, IL-6, and endotoxin levels were significantly higher in cirrhotic patients than in healthy subjects (7.3 +/- 0.2 versus 5.8 +/- 0.1 pg/ml, 6.4 +/ 0.8 versus 2.0 +/- 0.2 pg/ml, and 7.6 +/- 1.2 versus 2.8 +/- 0.3 pg/ml, respectively; p < 0.01). In cirrhotic patients the plasma levels of TNF-alpha IL-6, and endotoxin progressively increased in relation to the severity of liver dysfunction (graded by Pughs classification). A significant correlation was observed between plasma TNF-alpha and IL-6 levels (r = 0.48, p < 0.001), whereas no correlation was observed between plasma endotoxin levels and plasma TNF-alpha and IL-6 levels. Plasma IL-6 levels correlated negatively with systemic vascular resistance in patients with cirrhosis (r = 0.5, p < 0.01). CONCLUSIONS Plasma IL-6 levels are increased in patients with cirrhosis. The severity of liver cirrhosis is an important factor for the occurrence of increased IL-6 levels. IL-6 may play a role in the hyperdynamic circulation observed in patients with cirrhosis.

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.

Incidence of bleeding from gastroduodenal ulcers in patients with end-stage renal disease receiving hemodialysis

Background: Few large population-based studies have compared the incidence of bleeding of gastroduodenal ulcers between patients with and without end-stage renal disease. We investigated the association between ulcer bleeding and end-stage renal disease in patients receiving hemodialysis, and we sought to identify risk factors for ulcer bleeding. Methods: We performed a nationwide seven-year population study using data from the National Health Insurance Research Database in Taiwan. We identified 36 474 patients with end-stage renal disease who were receiving hemodialysis, 6320 patients with chronic kidney disease and 36 034 controls matched for age, sex and medication use. We performed log-rank testing to analyze differences in survival time without ulcer bleeding among the three groups. We performed Cox proportional hazard regressions to evaluate the risk factors for ulcer bleeding among the three groups and to identify risk factors in patients receiving hemodialysis. Results: Patients receiving hemodialysis and those with chronic kidney disease had a significantly higher incidence of ulcer bleeding than controls had (p < 0.001). Hemodialysis (hazard ratio [HR] 5.24, 95% confidence interval [CI] 4.67–5.86) and chronic kidney disease (HR 1.95, 95% CI 1.62–2.35) were independently associated with an increased risk of ulcer bleeding. Diabetes mellitus, coronary artery disease, cirrhosis and use of nonsteroidal anti-inflammatory drugs were risk factors for ulcer bleeding in patients with end-stage renal disease who were receiving hemodialysis Interpretation: Patients with end-stage renal disease who are receiving hemodialysis had a high risk of ulcer bleeding. Diabetes mellitus, coronary artery disease, cirrhosis and the use of nonsteroidal anti-inflammatory drugs were important risk factors for ulcer bleeding in these patients.

Proposal of a modified Child-Turcotte-Pugh scoring system and comparison with the model for end-stage liver disease for outcome prediction in patients with cirrhosis.

The model for end‐stage liver disease (MELD) has a better predictive accuracy for survival than the Child‐Turcotte‐Pugh (CTP) system and has been the primary reference for organ allocation in liver transplantation. The CTP system, with a score range of 5–15, has a ceiling effect that may compromise its predictive power. In this study, we proposed a refined CTP scoring method and investigated its predictive ability. An additional point was given to patients with serum albumin < 2.3 g/dL, bilirubin > 8 mg/dL or prothrombin time prolongation > 11 seconds. The modified CTP system, containing class D, was compared to the MELD and original CTP system in 436 patients. There was a significant correlation between the MELD and modified CTP score (ρ=0.59, P< 0.001). Using mortality as the endpoint, the area under receiver operating characteristic curve for modified CTP system was 0.895 compared with 0.872 for MELD (P=0.450) and 0.809 for original CTP system (P < 0.001) at 3 months; the area was 0.890, 0.837 and 0.756, respectively (P=0.051 and < 0.001, respectively) at 6 months. The risk ratio per unit increase for the modified CTP score was 2.7 and 3.08 at 3 and 6 months respectively (P < 0.001). In conclusion, the modified CTP system can be proposed as an alternative prognostic model for cirrhotic patients. By extending the score range according to the influence of the laboratory‐derived variables, the modified CTP system has a better performance than the original system and is as efficient as the MELD for outcome prediction. Liver Transpl 12:65–71, 2006.

An endoscopic injection with N-butyl-2-cyanoacrylate used for colonic variceal bleeding: a case report and review of the literature

We report a 64-yr-old patient with liver cirrhosis and bleeding esophageal varices that were obliterated by repeated endoscopic sclerotherapy. Eleven years later, he developed a massive, life-threatening rectosigmoid variceal hemorrhage. An endoscopic injection with N-butyl-2-cyanoacrylate (Histoacryl), performed over the rectosigmoid varices, achieved temporary hemostasis. The etiology, prevalence, relationship with portal hypertension, diagnosis, and treatment of colorectal varices are discussed.

Recurrence of esophageal varices following endoscopic treatment and its impact on rebleeding: comparison of sclerotherapy and ligation

BACKGROUND/AIMS Endoscopic variceal ligation is superior to sclerotherapy because of its lower rebleeding and complication rates. However, ligation is not without drawbacks due to a higher tendency to variceal recurrence. We conducted a randomized cohort study to delineate the long-term history of variceal recurrence following ligation and sclerotherapy, and to clarify the impact of recurrence on rebleeding and on the consumption of endoscopic treatment resources. METHODS Two hundred cirrhotic patients with esophageal variceal bleeding were randomized to undergo maintenance endoscopic variceal sclerotherapy or ligation. RESULTS One hundred and forty-one patients achieved variceal eradication and were regularly followed up for 2.2 to 6.7 (mean: 5.1 +/- 1.2) years. The demographic data, hepatic reserve, bleeding severity, and endoscopic features of both sclerotherapy (n=70) and ligation (n=71) showed no difference. Forty (57.1%) patients who underwent sclerotherapy experienced 58 recurrences of esophageal varices, in contrast to the 46 (64.8%) patients who underwent ligation and experienced 81 episodes of recurrence. Kaplan-Meier analysis showed that within 2 years variceal recurrence was more frequent for ligation than sclerotherapy, and the difference decreased thereafter. Multiple recurrence appeared more common with ligation (1/2/3/4/5 episodes of recurrence: 46/23/8/3/1 vs. 40/14/3/1/0, p=0.08). On multifactorial analysis, the endoscopic treatment method and red wale markings were the two factors determining variceal recurrence. Rebleeding from recurrent esophageal varices was unusual and showed no difference between the two groups (7/58 vs. 6/81, p>0.05). Rebleeding from gastric varices was more common after eradication by sclerotherapy (7/19 vs. 1/16, p=0.085) than by ligation. The number of sessions required for eradication of recurrent varices was no different between the two groups. CONCLUSIONS Early recurrence and multiple recurrence of esophageal varices are more likely in patients undergoing endoscopic ligation, compared to sclerotherapy; however, the recurrence did not lead to a higher risk of rebleeding or require more endoscopic treatment.

Plasma endothelin levels in patients with cirrhosis and their relationships to the severity of cirrhosis and renal function

BACKGROUND/AIMS Increased plasma endothelin levels have been reported in patients with cirrhosis. However, the relationship between plasma endothelin concentrations and hyperdynamic circulation or renal functions has not been documented. METHODS We measured the plasma endothelin-1 and endothelin-3 concentrations using radioimmunoassay in 96 patients with cirrhosis (Pughs A in 26, Pughs B in 45 and Pughs C in 25) and compared these values to 56 age- and sex-matched healthy subjects. Systemic and portal hemodynamic measurements, effective renal plasma flow, creatinine clearance, plasma aldosterone concentration and plasma renin activity were recorded for each patient. RESULTS Plasma endothelin-1 and endothelin-3 levels were significantly increased in patients with cirrhosis compared to healthy subjects. Additionally, plasma endothelin-1 and endothelin-3 values were higher in patients with cirrhosis and ascites than in those without ascites. Moreover, plasma endothelin-1 levels increased in relation to the severity of cirrhosis. On the other hand, modest negative correlations were found between endothelin-1 and creatinine clearance or effective renal plasma flow. CONCLUSIONS Plasma endothelin-1 and endothelin-3 levels are increased in patients with cirrhosis compared to healthy subjects. The increase in plasma endothelin-1 levels is related at least in part to the severity of cirrhosis. Increased endothelin-1 levels may possibly contribute to renal dysfunction in patients with cirrhosis.