Wei-Lun Tsai

Improved survival in patients receiving medical therapy as compared with banding ligation for the prevention of esophageal variceal rebleeding

Both medical therapy and endoscopic variceal ligation (EVL) have proven to be comparable in the prevention of variceal rebleeding. However, the long‐term results are still lacking. Our previous study enrolled 121 patients with history of esophageal variceal bleeding and randomized to receive EVL (EVL group, 60 patients) or drug therapy, nadolol plus isosorbide‐5‐mononitrate (N+I) (N+I group, 61 patients) to prevent variceal rebleeding. The EVL group received ligation regularly until variceal obliteration. The N+I group received N+I during the study period. Patients were followed for up to 8 years. After a median follow‐up of 82 months, recurrent upper gastrointestinal bleeding developed in 28 patients (47%) in the EVL group and 49 patients (80%) in the N+I group (P = 0.001). Recurrent bleeding from esophageal varices occurred in 18 patients (30%) in the EVL group and 39 patients (64%) in the N+I group. The actuarial probability of rebleeding from esophageal varices was lower in the EVL group (P = 0.001). A total of 42 patients of the EVL group and 30 patients of the N+I group died (P = 0.013). The multivariate Cox analysis indicated that age, serum albumin, presence of encephalopathy, and treatment were the factors predictive of mortality. Conclusion: Our long‐term follow‐up study showed that combination of N+I therapy was inferior to banding ligation in the reduction of variceal rebleeding, but with enhanced survival. (HEPATOLOGY 2008;48:580–587.)

Risk factors for ulcer development in patients with non-ulcer dyspepsia: a prospective two year follow up study of 209 patients

Background and aims: A subset of non-ulcer dyspepsia (NUD) disorders can evolve into peptic ulcer disease. This prospective study attempted to determine the independent risk factors for ulcer formation in NUD patients, and compared the natural history of Helicobacter pylori positive and negative NUD subjects. Methods: From May 1997 to April 1999, consecutive NUD patients were enrolled into the study. Endoscopy was performed routinely on enrolment, at the end of the second and 12th months, and whenever there was a dyspepsia attack. Patients were prospectively followed up for two years. Results: Peptic ulcers occurred in 16 of 209 NUD patients during the two year follow up period. Multivariate analysis of 13 host and bacterial factors demonstrated that advanced age (odds ratio 2.90), H pylori infection (odds ratio 3.59), and use of non-steroidal anti-inflammatory drugs (NSAID; odds ratio 4.46) were independently significant in predicting subsequent peptic ulcer development. NUD patients with all three risk factors had a 75% (3/4) risk of developing peptic ulcer but the ulcer incidence in patients without any of the risk parameters was only 1.2% (1/84). The resolution rate of symptoms in the H pylori positive NUD patients was similar to the H pylori negative patients (57.9% v 49.1%; 95% confidence interval (CI) −5 to 22). However, rates for subsequent peptic ulcer and erosion development were significantly higher in H pylori positive patients than in H pylori negative patients (ulcer 12.6% v 3.5%, 95% CI 1–16; erosion 23.2% v 12.3%, 95% CI 1–21). Conclusion: A small but significant proportion of NUD patients develop peptic ulcer after long term follow up. H pylori infection, NSAID use, and advanced age are independent risk factors for subsequent ulcer formation. Follow up endoscopy is strongly indicated for an NUD patient with multiple risk factors for ulcer formation when symptoms recur.

Effect of intravenous albumin on endotoxin removal, cytokines, and nitric oxide production in patients with cirrhosis and spontaneous bacterial peritonitis.

Objective. In patients with cirrhosis and spontaneous bacterial peritonitis (SBP), the use of intravenous albumin has been shown to prevent deterioration of renal function and to decrease the mortality rate, but the mechanisms remain unclear. The purpose of this study was to characterize the mechanisms of action of albumin with the focus on endotoxin and cytokines. Material and methods. Thirty patients with SBP were divided into two groups. Group 1 received antibiotics and albumin infusion (20% 50 cc every day for 3 days) and Group 2 received antibiotic treatment only. Twenty-four cirrhotic patients with sterile ascites were enrolled in Group 3 and received albumin infusion (20% 50 cc every day for 3 days). Plasma and ascitic fluid concentrations of endotoxin, nitric oxide products (NOx), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 were analyzed before and after treatments, respectively. Results. Combination therapy of albumin and antibiotics can significantly (p<0.01) reduce plasma levels of TNF-α and IL-6, and ascitic fluid levels of endotoxin, TNF-α and IL-6 in cirrhotic patients with SBP. Without the addition of albumin to an antibiotic regimen, the plasma and ascitic fluid levels of NOx increased significantly in patients with SBP (p=0.005 and p=0.004, respectively). Conclusions. The results confirm that the beneficial effects of albumin are related to the reduction of the levels of TNF-α and NOx in both plasma and ascitic fluid. The infusion of albumin continuously for 3 days in addition to antibiotic treatment at the time of SBP detection is recommended as an effective therapy for patients with cirrhosis and SBP.

Endoscopic papillary large balloon dilation alone without sphincterotomy for the treatment of large common bile duct stones

BackgroundLethal pancreatitis has been reported after treatment for common bile duct stones using small endoscopic papillary balloon dilation.MethodsWe retrospectively evaluated the safety and efficacy of using large balloon dilation alone without the use of sphincterotomy for the treatment of large common bile duct stones in Kaohsiung Veterans General Hospital. Success rate of stone clearance, procedure-related adverse events and incidents, frequency of mechanical lithotripsy use, and recurrent stones were recorded.ResultsA total of 247 patients were reviewed in the current study. The mean age of the patients was 71.2 years. Most of them had comorbidities. Mean stone size was 16.4 mm. Among the patients, 132 (53.4%) had an intact gallbladder and 121 (49%) had a juxtapapillary diverticulum. The mean size of dilating balloon used was 13.2 mm. The mean duration of the dilating procedure was 4.7 min. There were 39 (15.8%) patients required the help of mechanical lithotripsy while retrieving the stones. The final success rate of complete retrieval of stones was 92.7%. The rate of pancreatic duct enhancement was 26.7% (66/247). There were 3 (1.2%) adverse events and 6 (2.4%) intra-procedure bleeding incidents. All patients recovered completely after conservative and endoscopic treatment respectively, and no procedure-related mortality was noted. 172 patients had a follow-up duration of more than 6 months and among these, 25 patients had recurrent common bile duct stones. It was significantly correlated to the common bile duct size (p = 0.036)ConclusionsEndoscopic papillary large balloon dilation alone is simple, safe, and effective in dealing with large common bile duct stones in relatively aged and debilitated patients.

Low-dose terlipressin plus banding ligation versus low-dose terlipressin alone in the prevention of very early rebleeding of oesophageal varices.

Background: Very early rebleeding is frequently encountered in patients with acute oesophageal variceal bleeding. A trial was designed to assess the efficacy and safety in patients with no active bleeding at endoscopy, receiving banding ligation association with terlipressin to prevent very early rebleeding. Methods: Patients with no active variceal bleeding at endoscopy were evaluated. Eligible patients were randomised to receive terlipressin infusion alone for 5 days (Terlipressin group) or banding ligation plus terlipressin infusion for 2 days (Combined group). Primary endpoints were treatment failure and very early rebleeding. Results: The terlipressin group was composed of 46 patients and the Combined group was composed of 47 patients. Both groups were comparable in terms of baseline data. Forty-eight-hour haemostasis was achieved in 91% in the Terlipressin group and 98% in the Combined group (p = 0.20). Very early rebleeding within 48–120 h occurred in 7 patients (15%) in the Terlipressin group but not in any patients (0%) in the Combined group (p = 0.006). Treatment failure was 24% in the Terlipressin group and 2% in the Combined group (p = 0.002). Multivariate analysis revealed that treatment (OR 0.081; 95% CI 0.010 to 0.627) was the only predictive factor of very early rebleeding. Blood requirement was significantly lower in the Combined group than in the Terlipressin group. Complications and 6-week survival were similar in both groups. Conclusions: Combination of banding ligation and terlipressin infusion for 2 days was superior to only infusion of terlipressin for 5 days in the reduction of very early rebleeding and treatment failure in patients with inactive variceal bleeding at endoscopy. Trial registration number: ISRCTN28353453

A randomized, controlled trial of banding ligation plus drug therapy versus drug therapy alone in the prevention of esophageal variceal rebleeding

Background & Aims:  Both medications with beta‐blockers and isosorbide‐5‐mononitrate and endoscopic variceal ligation have been proven plausible in the prevention of variceal rebleeding. However, the relative efficacy and safety of the combined treatment for preventing rebleeding remains unresolved.

Suppressor of Cytokine Signaling 3 Suppresses Hepatitis C Virus Replication in an mTOR-Dependent Manner

ABSTRACT We and others have observed that hepatic levels of suppressor of cytokine signaling 3 (SOCS3) are significantly higher in persons with chronic hepatitis C, particularly those who are nonresponders to interferon (IFN) treatment, than in healthy individuals. However, the relationship between SOCS3 and hepatitis C virus (HCV) replication remains unclear. Given its putative role, we hypothesized that SOCS3 is permissive for viral replication. We therefore used the OR6 cell line, which harbors a genotype 1b full-length HCV replicon, and the genotype 2a full-length HCV strain JFH1 infection system to analyze the effects of SOCS3 overexpression and short hairpin RNA (shRNA)-mediated knockdown on HCV replication. We further analyzed the role of mTOR in the effects of SOCS3 by treating selected cells with rapamycin. OR6 cells and JFH1-infected Huh7.5.1 cells expressed significantly less SOCS3 than control cells. Furthermore, inhibition of HCV replication with the HCV protease inhibitor BILN 2061 restored SOCS3 protein levels. SOCS3 overexpression in OR6 cells and JFH1-infected Huh7.5.1 cells resulted in significantly lower HCV replication than that in the control cells, despite SOCS3-related inhibition of STAT1 phosphorylation and type I IFN signaling. In contrast, JFH1-infected cells with stable SOCS3 knockdown expressed higher levels of HCV proteins and RNA than did control cells. SOCS3-targeting shRNA also knocked down mTOR and phospho-mTOR. The mTOR inhibitor rapamycin reversed the inhibitory effects of SOCS3. In independent investigations, SOCS3 unexpectedly suppressed HCV replication in an mTOR-dependent manner. These findings suggest that increased SOCS3 levels consistently observed in chronic IFN nonresponders may reflect a compensatory host antiviral response to persistent infection and that manipulation of SOCS3/mTOR may offer benefit against HCV infection.

The characteristics and the prognosis for patients presenting with actively bleeding esophageal varices at endoscopy

BACKGROUND It remains unresolved whether the prognosis is worse for patients who present with actively bleeding varices at endoscopy compared with those in whom variceal bleeding has stopped. METHODS Patients with acute esophageal variceal bleeding were enrolled in this study and were divided into two groups: an active bleeding group and an inactive bleeding group. All patients had band ligation shortly after endoscopic examination and underwent elective ligation procedures until the varices were obliterated. Patients were followed for 1 year or until death. Short- and long-term prognoses were compared. RESULTS The active bleeding group included 54 patients and the inactive bleeding included 251 patients. Initial hemostasis was achieved in 93% in the active group and 99% in the inactive group ( p = not significant). The rate of recurrent variceal bleeding within 30 days was 24% in the active bleeding group vs. 12% in the inactive bleeding group ( p = 0.01); the mortality rates were 18% and 8%, respectively ( p = 0.03 in a single statistical test; however, Bonferroni correction for the multiple testing of data removed this significance). The rate of recurrent variceal bleeding within 1 year was 37% in the active bleeding group and 27% in the inactive bleeding group ( p = 0.06); the mortality rates were 22% and 21%, respectively ( p = not significant). CONCLUSIONS Whether variceal bleeding is active or inactive at endoscopy, variceal ligation is equally effective for control of bleeding. The rates of recurrent bleeding and mortality at 1 month were significantly higher among patients with active bleeding. However, the mortality rate was similar for both groups at 1 year.

Clinical trial: percutaneous acetic acid injection vs. percutaneous ethanol injection for small hepatocellular carcinoma--a long-term follow-up study.

Aliment Pharmacol Ther 28, 304–311

Emergency endoscopic variceal ligation versus somatostatin for acute esophageal variceal bleeding.

Background: Endoscopic variceal ligation and somatostatin are widely used for treating acute esophageal variceal bleeding. This study compared the efficacy, safety, and survival of both therapies. Methods: Acute esophageal variceal bleeding patients were randomized to undergo emergency ligation or receive a bolus of 250 μg somatostatin plus infusion at 250 μg/hour for 48 hours and undergo ligation subsequently. Results: Three (4.8%) of 62 patients in the ligation group and 20 (31.7%) of 63 patients in the somatostatin group encountered treatment failure (p = 0.0001). Transfusion requirements were 4.7 ± 3.2 units in the ligation group and 6.9 ± 7.3 units in the somatostatin group (p = 0.03). Hospital stay was 7.7 ± 4.0 days in the ligation group and 10.2 ± 9.9 days in the somatostatin group (p = 0.07). Adverse effects occurred in the ligation group (20 episodes) and the somatostatin group (27 episodes) (p = 0.2). The 42‐day mortality rates were 5 patients (8.1%) in the ligation group and 3 patients (4.8%) in the somatostatin group (p = 0.5). Conclusion: Emergency ligation was superior to somatostatin in treating acute esophageal variceal bleeding, with fewer requirements of transfusion and a tendency toward shorter hospital stay. The adverse effects and 42‐day mortality rates were similar between both treatments.