Long-term outcome after antiviral therapy of patients with hepatitis C virus infection and decompensated cirrhosis.

BACKGROUND & AIMS: We evaluated the long-term outcomes after antiviral therapy of patients with decompensated cirrhosis and hepatitis C virus (HCV) infection. METHODS: Seventy-five patients with HCV infection and decompensated cirrhosis received therapy with peginterferon alfa-2b and ribavirin. We compared adverse-event profiles and mortality rates between patients with or without sustained virologic responses (SVRs). The mean follow-up time off therapy was 51 ± 18 months (range, 3-78 months). RESULTS: Seven patients with HCV genotypes 1 or 4 (16%) and 17 patients with genotypes 2 or 3 (55%) achieved SVRs. The mean survival times were 53 months among patients who did not achieve SVRs (95% confidence interval [CI], 48-59 months) and 73 months among those who did achieve SVRs (95% CI, 67-80 months) (P = .004). During the study, 25 patients died (2 with and 23 without SVRs). During the follow-up period, 8 of 24 patients with SVRs (33.3%) and 49 of 51 without SVRs (96.1%) experienced further events of decompensation (P < .0001). The hospital readmission rates for patients with and without SVRs were 7.4 and 56 per 1000 person-months, respectively (ratio of 7.5 without/with SVR; 95% CI, 4.0-16.0; P < .0001). At the end of the follow-up period, the incidence of hepatocellular carcinoma was not associated with clearance of HCV. CONCLUSIONS: Among patients with cirrhosis that is a result of HCV infection and who have progressed to a stage of liver decompensation, an SVR after antiviral therapy is a positive prognostic factor.

High- versus low-dose proton pump inhibitors after endoscopic hemostasis in patients with peptic ulcer bleeding: a multicentre, randomized study.

BACKGROUND: The most effective schedule of proton pump inhibitor (PPI) administration following endoscopic hemostasis of bleeding ulcers remains uncertain. METHODS: Patients with actively bleeding ulcers and those with nonbleeding visible vessel or adherent clot were treated with epinephrine injection and/or thermal coagulation, and randomized to receive intravenous PPIs according to an intensive regimen (80 mg bolus followed by 8 mg/h as continuous infusion for 72 h) or a standard regimen (40 mg bolus daily followed by saline infusion for 72 h). After the infusion, all patients were given 20 mg PPI twice daily orally. The primary end point was the in-hospital rebleeding rate, as ascertained at the repeat endoscopy. RESULTS: Bleeding recurred in 28 of 238 patients (11.8%) receiving the intensive regimen, and in 19 of 236 (8.1%) patients receiving the standard regimen (P= 0.18). Most rebleeding episodes occurred during the initial 72-h infusion: 18 (7.6%) and 19 events (8.1%) in the intensive and standard groups, respectively (P= 0.32). Mean units of blood transfused were 1.7 +/- 2.1 in the intensive and 1.5 +/- 2.1 in the standard regimen group (P= 0.34). The duration of hospital stay was <5 days for 88 (37.0%) and 111 patients (47.0%) in the intensive and standard groups (P= 0.03). There were fewer surgical interventions in the standard versus intensive regimen (1 vs 3). Five patients in each treatment group died. CONCLUSIONS: Following endoscopic hemostasis of bleeding ulcers, standard-dose PPIs infusion was as effective as a high-dose regimen in reducing the risk of recurrent bleeding. (ClinicalTrials.gov number, NCT00374101).

Pancreatic duct stents in the prophylaxis of pancreatic damage after endoscopic retrograde cholangiopancreatography: a systematic analysis of benefits and associated risks.

METHODS: The efficacy of pancreatic stenting in the prevention of pancreatitis following endoscopic retrograde cholangiopancreatography (ERCP) was evaluated by a meta-analysis of 6 controlled studies; 12 additional uncontrolled studies were analyzed for rates of associated risk. RESULTS: Post-ERCP pancreatitis (PEP) developed in 16.5% of controls, and in 5.1 or 9.6% of the stent group at the per-protocol (PP) or intention-to-treat (ITT) analyses. By analyzing only the 4 randomized trials, PEP developed in 24.1% of controls, and in 6.1 or 12.0% of the stented patients at the PP or ITT analyses. Risk was significantly lower in the stent group when compared with controls: OR 0.44 (95% CI 0.24-0.81). The absolute risk reduction is 12.0 (95% CI 3.0-21.0), the number needed to treat 8 (95% CI 5-34), and the publication bias 2. ORs for mild to moderate PEP were reduced in the stent group (OR = 0.537, 95% CI 0.283-1.021), as were those for severe PEP (OR = 0.123, 95% CI 0.021-0.726). Non-pancreatic complications were 4.2%, and included early stent migration (1.4%), perforations (0.4%), bleeding (1.4%), and infections (1.0%). CONCLUSION: Available trials show benefit for pancreatic stenting in the prophylaxis of PEP, but more randomized studies are needed before endorsing a routine use of this endoscopic procedure.

Antisecretory vs. antiproteasic drugs in the prevention of post-ERCP pancreatitis: the evidence-based medicine derived from a meta-analysis study.

Uncertainties still exist about the clinical benefit of pharmacological prevention of post-ERCP pancreatitis by either antisecretory drugs such as somatostatin and its long-acting analogue octreotide, or protease inhibitors such as gabexate mesilate. Recent, large-scale prospective studies have reported a fourfold reduction in acute pancreatitis as compared to a placebo with the prophylactic administration of either gabexate mesilate or somatostatin, whereas octreotide was found to be ineffective. An initial meta-analysis of all available controlled trials on this topic has confirmed these findings. The indiscriminate use of these drugs in all patients is unlikely to be cost-effective, but the selective use of prophylaxis for high-risk patients might be advocated. Moreover, inasmuch as 85% of complications developed within 4 to 6 hours of completing the ERCP, it would be reasonable to infuse drugs only for this limited length of time. A recent prospective trial, carried out on high-risk patients, has surprisingly documented a higher incidence, although a non-significant one, of pancreatitis in patients who received short-term prophylaxis with somatostatin or gabexate mesilate than those given a placebo: 11.5% and 8.1% vs. 6.5%, respectively. In order to explore this discrepancy, the original meta-analysis was updated by including data of this negative trial: heterogeneity among the trials was apparent. A careful scrutiny of the most recent studies has revealed differences in patient population, protocols of drug administration, technique and operator-related risk factors for complications among the trials, which could explain, by themselves, the contrasting results reported by the interventional studies. In conclusion, current literature does not support the prophylactic use of either somatostatin or gabexate mesilate for the prevention of ERCP-related pancreatic damage, even in patients deemed to be at high risk for complications. At present, post-ERCP complications (and pancreatitis) can be prevented efficaciously by appropriate selection of patients, mastering of the technique and operator competence.

How evidence-based are current guidelines for managing patients with peptic ulcer bleeding?

Current guidelines for managing ulcer bleeding state that patients with major stigmata should be managed by dual endoscopic therapy (injection with epinephrine plus a thermal or mechanical modality) followed by a high dose intravenous infusion of proton pump inhibitors (PPIs). This paper aims to review and critically evaluate evidence supporting the purported superiority of a continuous infusion over less intensive regimens of PPIs administration and the need for adding a second hemostatic endoscopic procedure to epinephrine injection. Systematic searches of PubMed, EMBASE and the Cochrane library were performed. There is strong evidence for an incremental benefit of PPIs over H2-receptor antagonists or placebo for the outcome of patients with peptic ulcer bleeding following endoscopic hemostasis. However, the benefit of PPIs is unrelated to either the dosage (intensive vs standard regimen) or the route of administration (intravenous vs oral). There is significant heterogeneity among the 15 studies that compared epinephrine with epinephrine plus a second modality, which might preclude the validity of reported summary estimates. Studies without second look endoscopy plus re-treatment of re-bleeding lesions showed a significant benefit of adding a second endoscopic modality for hemostasis, while studies with second-look and re-treatment showed equal efficacy between endoscopic mono and dual therapy. Inconclusive experimental evidence supports the current recommendation of the use of dual endoscopic hemostatic means and infusion of high-dose PPIs as standard therapy for patients with bleeding peptic ulcers. Presently, the combination of epinephrine monotherapy with standard doses of PPIs constitutes an appropriate treatment for the majority of patients.

Continuous infusion versus bolus administration of steroids in severe attacks of ulcerative colitis: a randomized, double-blind trial.

BACKGROUND: In patients with severe attacks of ulcerative colitis (UC), IV steroids represent the first-line treatment, leading to clinical improvement in approximately 50-60% of patients. AIM: The aim of this study was to prospectively compare the efficacy and safety of different modalities of steroid administration, and to evaluate predictors of failure to therapy. MATERIALS AND METHODS: In a single-center, double-blind trial, consecutive patients with a severe attack of UC received 1 mg/kg/day of 6-methyl-prednisolone administered randomly by either a bolus injection (group A) or continuous infusion (group B). RESULTS: Sixty-six patients were enrolled (35 men, mean age 38 +/- 15, range 18-75 yr), 15 of them at their first attack of UC; in the remaining cases, the mean duration of disease was 4.5 +/- 5 yr. At inclusion, forty patients (60%) had pancolitis and the remainder had left-sided colitis. Overall, thirty-three patients (50%) underwent clinical remission after 7 days of treatment: 16 of 32 in group A and 17 of 34 in group B. Thirty-one patients eventually underwent total colectomy (12 in group A and 9 in group B), which was carried out by the first month in 10 patients (5 in each group). Twenty-eight patients (15 in group A and 13 in group B) experienced steroid-related adverse reactions. All differences between groups were not statistically significant. Previous use of steroids (OR 13.6, CI 2-86) and active smoking (OR 11.6, CI 1.4-107) were independent predictors of nonresponse. CONCLUSIONS: In severe attacks of UC, methyl-prednisolone given as a continuous infusion was no better than bolus administration in terms of efficacy and safety.

Peginterferon alfa-2b and ribavirin in patients with hepatitis C virus and decompensated cirrhosis: a controlled study.

BACKGROUND/AIM: To evaluate long-term outcomes in decompensated HCV-related cirrhotic patients treated with antiviral therapy. METHODS: Of 129 eligible patients, 66 received peginterferon alfa-2b and ribavirin for 24 weeks, and 63 were controls. Survival and recurrence of liver failure events after therapy were main outcomes. RESULTS: Therapy was tolerated by 27 patients, dose reduced in 26 for toxicity, and discontinued in 13 for intolerance. End-of-therapy and sustained virological response (SVR) rates were 82.6% and 43.5% for HCV 2/3 patients, and 30.2% and 7.0% for HCV 1/4 patients. During therapy, odds ratios for severe infections or deaths due to infection were 2.95 (95% C.I. 0.93-9.3) and 1.97 (95% C.I. 0.40-9.51) in treated patients as compared with controls. During a follow-up of 30 months off-therapy, decompensated events occurred in 52, 33, and 3 of controls, non-responders, and SVR patients. Odds ratios for ascites, encephalopathy, and oesophageal bleeding in treated patients significantly decreased as compared with controls. Annualized incidence of death was 2.34, 1.91, and 0 per 1000 patient-years, respectively, in controls, non-responders, and SVR patients. Survival curves showed early separation of SVR patients from both non-responders and controls at approximately 6 months. CONCLUSIONS: In decompensated cirrhotics, HCV clearance by therapy is life-saving and reduces disease progression.