High incidence of mortality and recurrent bleeding in patients with Helicobacter pylori-negative idiopathic bleeding ulcers.

BACKGROUND & AIMS: The long-term prognosis of peptic ulcers associated with neither Helicobacter pylori nor nonsteroidal anti-inflammatory drugs (NSAIDs) is unknown. METHODS: This 7-year prospective cohort study recruited patients with bleeding ulcers from January to December 2000. H pylori-negative idiopathic bleeding ulcers were defined as having tested negative for H pylori, having no exposure to aspirin or analgesics within 4 weeks before endoscopy, and having no other identifiable causative factors. After ulcers healed, patients were divided into 2 groups: patients with prior H pylori-negative idiopathic bleeding ulcers (H pylori-negative idiopathic ulcer cohort; n = 120) and those with H pylori-positive, NSAID-negative bleeding ulcers who received eradication therapy (H pylori ulcer cohort; n = 213). Both groups were followed for

Combination of a cyclo-oxygenase-2 inhibitor and a proton-pump inhibitor for prevention of recurrent ulcer bleeding in patients at very high risk: a double-blind, randomised trial.

BACKGROUND: Guidelines on pain management recommend that patients at risk of ulcers receive either a cyclo-oxygenase (COX 2) inhibitor or a non-steroidal anti-inflammatory drug (NSAID) with a proton-pump inhibitor (PPI). These two treatments have similar effectiveness, but they are insufficient for protection of patients at very high risk for ulcer bleeding. We aimed to test the hypothesis that in patients with previous ulcer bleeding induced by non-selective NSAIDs, combined treatment with the COX 2 inhibitor celecoxib and the PPI esomeprazole would be better than celecoxib alone for prevention of recurrent ulcer bleeding. METHODS: 441 consecutively presenting patients who were taking non-selective NSAIDs for arthritis were recruited to our single-centre, prospective, randomised, double-blind trial after admission to hospital with upper-gastrointestinal bleeding. Patients were enrolled after their ulcers had healed and a histological test for Helicobacter pylori was negative. All patients were given 200 mg celecoxib twice daily. 137 patients were randomly assigned to receive 20 mg esomeprazole twice daily (combined-treatment group), and 136 to receive a placebo (control group) for 12 months. The primary endpoint was recurrent ulcer bleeding during treatment or within 1 month of the end of treatment. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00365313. FINDINGS: Combination treatment was more effective than celecoxib alone for prevention of ulcer bleeding in patients at high risk. The 13-month cumulative incidence of the primary endpoint was 0% in the combined-treatment group and 12 (8.9%) in the controls (95% CI difference, 4.1 to 13.7; p=0.0004). The median follow-up was 13 months (range 0.4-13.0). Discontinuation of treatment and the incidence of adverse events were similar in the two treatment groups. INTERPRETATION: Patients at very high risk for recurrent ulcer bleeding who need anti-inflammatory analgesics should receive combination treatment with a COX 2 inhibitor and a PPI. Our findings should encourage guideline committees to review their recommendations for patients at very high risk of recurrent ulcer bleeding.

A randomized, controlled trial of combination therapy for chronic hepatitis B: comparing pegylated interferon-alpha2b and lamivudine with lamivudine alone.

BACKGROUND: Conventional interferon and lamivudine monotherapy are unsatisfactory in treating hepatitis B virus (HBV) infection. OBJECTIVE: To evaluate the efficacy and safety of pegylated interferon-alpha2b and lamivudine combination therapy for chronic hepatitis B. DESIGN: Randomized, controlled, open-label trial. SETTING: Outpatient clinic in a referral center. PARTICIPANTS: 100 treatment-naive patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B and moderately elevated alanine aminotransferase levels. MEASUREMENT: The primary end point was sustained virologic response (HBeAg seroconversion and HBV DNA level < 500,000 copies/mL) at 24 weeks after cessation of treatment. INTERVENTION: A staggered regimen of combination therapy with pegylated interferon-alpha2b (1.5 microg/kg of body weight per week; maximum, 100 microg) given for 32 weeks plus lamivudine (100 mg daily) given for 52 weeks versus lamivudine (100 mg daily) monotherapy given for 52 weeks. Of the 100 participants, 96% completed treatment and 80% completed post-treatment follow-up. RESULTS: The rate of sustained virologic response was 36% for the combination treatment group and 14% for the lamivudine monotherapy group (absolute difference, 22 percentage points [95% CI, 6 to 38 percentage points]). End-of-treatment outcomes showed that, compared with monotherapy, patients receiving combination therapy more often had virologic response (60% vs. 28% [absolute difference, 32 percentage points (CI, 14 to 50 percentage points)]); had more substantial reductions of HBV DNA (3.91 log10 copies/mL vs. 2.83 log10 copies/mL); and less often had lamivudine-resistant mutants (21% vs. 40%). The percentages of patients with normalization of alanine aminotransferase levels and histologic improvement did not differ. Adverse effects, such as transient influenza-like symptoms, alopecia, and local erythematous reactions, were more common with combination therapy. LIMITATIONS: This study lacked a double-blind design and was conducted at 1 institution. Because of the staggered pegylated interferon-lamivudine regimen, patients assigned to combination therapy received treatment for 8 weeks longer than those assigned to monotherapy. CONCLUSIONS: In patients with HBeAg-positive chronic hepatitis B, staggered combination treatment with pegylated interferon-alpha2b and lamivudine may lead to a higher rate of virologic response than lamivudine monotherapy.

Hepatitis B virus genotype has no impact on hepatitis B e antigen seroconversion after lamivudine treatment.

AIM: To investigate the association of hepatitis B virus (HBV) genotype and HBeAg seroconversion after nucleotide analogue treatment. METHODS: Chronic hepatitis B patients receiving lamivudine followed up for at least 6 months post-treatment were studied. Consecutive treatment-naïve patients who were prospectively followed up in the clinic for at least 18 months were studied as controls. HBeAg seroconversion was defined as loss of HBeAg, appearance of anti-HBe and normalization of alanine aminotransferase for at least 6 months. RESULTS: Thirty-five patients on lamivudine and 96 control patients followed up for 39 (18-49) months were studied. Lamivudine was given for 12 (10-18) months, and patients were followed up for 15 (6-34) months after drug cessation. Genotype B and C HBV were found in 43 and 88 patients and HBeAg seroconversion occurred in 12 (28%) and 16 (18%) patients, respectively (P=0.30). There was no difference in HBeAg seroconversion between patients infected by genotype B and C HBV in the control (35% vs 21%, P=0.25) and lamivudine-treated (14% vs 10%, P=1.00) groups. CONCLUSION: HBeAg seroconversion after treatment by lamivudine was not influenced by the HBV genotype.

Use of hepatitis B virus DNA quantitation to predict hepatitis B e antigen reversion in cases of chronic hepatitis B.

Seventy-three chronic hepatitis B patients who had either hepatitis B e antigen (HBeAg) seroconversion (group I) or HBeAg-negative disease (group II) were studied. HBV DNA levels at HBeAg seroconversion (group I) and at initial visits (group II) were significantly lower among patients who were persistently negative for HBeAg than among those who underwent HBeAg reversion.

Hepatitis B virus genotype C takes a more aggressive disease course than hepatitis B virus genotype B in hepatitis B e antigen-positive patients.

One hundred forty-six hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients were followed up for 32 +/- 13 months. All six patients with hepatocellular carcinoma had hepatitis B virus (HBV) genotype C. Disease activity was greater in patients infected by HBV genotype C than in those infected by HBV genotype B in the HBeAg-positive phase but not after HBeAg seroconversion.

Follow up of serial urea breath test results in patients after consumption of antibiotics for non-gastric infections.

AIM: The widespread use of antibacterial therapy has been suggested to be the cause for the decline in the prevalence of Helicobacter pylori infection. This study examine the serial changes of urea breath test results in a group of hospitalized patients who were given antibacterial therapy for non-gastric infections. METHODS: Thirty-five hospitalized patients who were given antibacterial therapy for clinical infections, predominantly chest and urinary infections, were studied. Most (91 %) patients were given single antibiotic of either a penicillin or cephalosporin group. Serial (13)C-urea breath tests were performed within 24 hours of initiation of antibiotics, at one-week and at six-week post-therapy. H. pylori infection was diagnosed when one or more urea breath tests was positive. RESULTS: All 35 patients completed three serial urea breath tests and 26 (74 %) were H. pylori-positive. Ten (38 %) H. pylori-infected patients had at least one negative breath test results during the study period. The medium delta (13)C values were significantly lower at baseline (8.8) than at one-week (20.3) and six-week (24.5) post-treatment in H. pylori-positive individuals (P=0.022). Clearance of H. pylori at six-week was only seen in one patient who had received anti-helicobacter therapy from another source. CONCLUSION: Our results suggested that one-third of H. pylori-infected individuals had transient false-negative urea breath test results during treatment with antibacterial agent. However, clearance of H. pylori infection by regular antibiotic consumption is rare.

Tuberculous peritonitis-associated mortality is high among patients waiting for the results of mycobacterial cultures of ascitic fluid samples.

We identified 60 cases of tuberculous peritonitis during the past 12 years at our health care center. Most of the patients had severe underlying medical conditions, such as cirrhosis, renal failure, diabetes mellitus, and malignancy. Abnormal chest radiograph findings, ascitic fluid lymphocytosis, and biochemical findings for exudates could only identify 33%, 37%, and 53% of the cases, respectively. On the other hand, peritoneal biopsy allowed early definitive diagnosis for 9 patients. Thirty-one patients died, 26 of whom died < or =6 weeks after their initial presentation, often before the result of mycobacterial culture was available. Only 8 patients died of advanced disease after antituberculous therapy was started. Univariate analysis showed that advanced age, underlying diagnosis, and delayed initiation of therapy were associated with higher mortality rates. Standard antituberculous chemotherapy is highly effective. However, conventional microbiologic diagnostic methods are slow and not sensitive enough for establishing a diagnosis of tuberculous peritonitis.

Survival and prognostic indicators in patients with hepatitis B virus-related cirrhosis after onset of hepatic decompensation.

GOALS: To determine the 2-year survival and prognostic indicators of hepatitis B virus-related cirrhosis after the onset of hepatic decompensation. BACKGROUND: Chronic hepatitis B (CHB) patients with cirrhosis and resultant hepatic decompensation have reduced survival. However, the natural history of these patients has not been well characterized in previous studies. Better understanding of survival and prognostic indicators is essential in management of these patients, especially in determining who should be candidates for orthotopic liver transplantation. STUDY: This is a retrospective longitudinal study of 96 patients with CHB-related cirrhosis after the onset of hepatic decompensation. The overall survival was ascertained, and clinical and laboratory variables were analyzed. Significant prognostic indicators for survival at 2 years were determined using univariate and multivariate analyses with Cox regression model. RESULTS: The overall survival was 80% at 2 years after onset of decompensation. With univariate and multivariate analyses, hepatic encephalopathy and hypoalbuminemia less than 2.8 g/dL were significant prognostic indicators of poor survival probability. The hazard ratios were 5.22 (95% confidence interval, 1.67-16.3) and 8.57 (95% confidence interval, 1.94-37.8), respectively. Patients with hypoalbuminemia less than 2.8 g/dL had a 2-year survival of only 62%. CONCLUSIONS: Our study showed that of CHB patients who developed the first episode of hepatic decompensation, those with hepatic encephalopathy or significant hypoalbuminemia or both have worse prognoses. They should be considered potential candidates for liver transplantation.