Background and aims: Liver steatosis is frequent in chronic hepatitis C, particularly in patients infected with hepatitis C virus (HCV) genotype 3. The aim of this study was to determine the ...relationship between steatosis and fibrosis in chronic hepatitis C as a function of viral genotype. Methods: A multivariable logistic regression analysis was carried out in 755 chronic hepatitis C patients (mean body mass index (BMI) 24.11 kg/m2; 178 with genotype 3), consecutively admitted to three referral hospitals. Liver histology showed steatosis in 315 and fibrosis in 605 patients, of whom 187 had cirrhosis (78 compensated and 109 decompensated). Results: Steatosis was independently associated with fibrosis (p<0.001), genotype 3 (p<0.001), BMI (p<0.001), ongoing alcohol abuse (p<0.001), and age (p = 0.001). Fibrosis was associated with the Metavir activity score (p<0.001), age (p<0.001), steatosis (p = 0.001), past alcohol abuse for >5 years (p = 0.015), and BMI (p = 0.034). When regression analysis was repeated on patients divided according to viral genotype (that is, 3 v non-3) to identify type specific risk factors, steatosis was associated with ongoing alcohol abuse (p<0.001) and age (p = 0.01) only in non-3 genotype infected patients and with Metavir activity (p = 0.044) only in genotype 3 infected patients. Similarly, fibrosis was associated with steatosis only in genotype 3 infected individuals (p = 0.018), and with past alcohol abuse (p = 0.003) and (marginally) diabetes (p = 0.078) only in non-3 genotype infected patients. Conclusions: Steatosis influences chronic hepatitis C progression in a genotype specific way. Patients infected with genotype 3 and histologically confirmed steatosis should not be deferred from effective antiviral therapy.
Background. Antibiotic-resistant
Helicobacter pylori strains are becoming increasingly prevalent, although it is not clear to what extent the new resistant organisms will spread.
Aim. To evaluate the ...incidence of secondary
Helicobacter pylori resistance to metronidazole, clarithromycin and/or amoxycillin after one-week proton pump inhibitor based triple therapy failure in patients who were, before therapy, infected with
Helicobacter pylori strains susceptible to these antibiotics.
Patients and Methods. Enrolled in the study were 97 consecutive
Helicobacter pylori positive subjects infected by
Helicobacter pylori strains susceptible to metronidazole, clarithromycin and amoxycillin. Activity of tested antibiotics was determined by means of the E-test. Patients were treated for seven days with a proton pump inhibitor, omeprazole 20 mg twice daily or pantoprazole 40 mg once daily, plus clarithromycin 250 mg twice daily and metronidazole 250 mg four times daily; or with a proton pump inhibitor plus amoxycillin 1 g twice daily and clarithromycin 500 mg twice daily. Two months after completion of therapy, endoscopy and gastric biopsies for histology, rapid urease test and culture were repeated.
Results. Four patients were dropped from the study. Overall
Helicobacter pylori cure rates expressed as both intention-to-treat and per-protocol analyses, were, respectively, 80% (
40
50
) and 81.6% (
40
49
) with proton pump inhibitor, clarithromycin and metronidazole and 76.6% (
36
47
) and 81.8% (
36
44
) with proton pump inhibitor, amoxycillin and clarithromycin. No significant differences were observed between the two treatments. Subjects in whom treatment failed were significantly younger and had less active ulcer than cured patients. Of treatment failures, 70.6% (12 out of 17 subjects) developed a secondary resistance to metronidazole (35.3%) and/or clarithromycin (64.7%). Secondary antibiotic resistance occurred in 77.8% of treatment failures treated with proton pump inhibitor, clarithromycin and metronidazole and in 62.5% of those treated with proton pump inhibitor, amoxycillin and clarithromycin. Considering all patients treated, the overall incidence of secondary metronidazole and/or clarithromycin resistance after therapy was reported in 12.9% of subjects (12 out of 93 treated patients).
Conclusions. Secondary
Helicobacter pylori resistances to metronidazole and/or clarithromycin occurred in large percentages in patients with treatment failure after the one-week proton pump inhibitor-based triple therapies, proton pump inhibitor, clarithromycin and metronidazole and proton pump inhibitor, amoxycillin and clarithromycin. It is likely that new antibiotics or treatment strategies will be needed in the near future to successfully treat
Helicobacter pylori infection.
Background
: Resistance of Helicobacter pylori to antibiotics may be a major reason for treatment failure.
Aim
: To evaluate the effect of primary H. pylori resistance to antibiotics on the cure ...rates of three anti‐H. pylori 1‐week triple therapies.
Methods
: One hundred and sixteen consecutive patients diagnosed H. pylori‐positive by gastric histology, rapid urease test and culture were enrolled. Activity of tested antibiotics was determined by means of the E‐test. Patients were treated for 7 days with: (i) pantoprazole 40 mg o.d. plus amoxycillin 1 g b.d. and metronidazole 250 mg q.d.s. (PAM); (ii) pantoprazole 40 mg o.d. plus clarithromycin 250 mg b.d. and metronidazole 250 mg q.d.s. (PCM); or (iii) pantoprazole 40 mg o.d. plus amoxycillin 1 g b.d. and clarithromycin 250 mg b.d. (PAC). Two months after completion of therapy, endoscopy and gastric biopsies were repeated.
Results
: Primary resistance rates to metronidazole, clarithromycin and amoxycillin were 17.2, 6.9 and 0%, respectively. Overall H. pylori cure rates expressed as intention‐to‐treat and per protocol analyses were, respectively, 79% and 86% with PAM, 82% and 89% with PCM, and 85% and 85% with PAC. Significantly lower cure rates were observed in metronidazole‐resistant patients treated with PAM (56% vs. 96%, P = 0.01) or PCM (50% vs. 97%, P = 0.01). A trend towards lower H. pylori cure rates was observed in clarithromycin‐resistant patients treated with PCM (67% vs. 91%, P = 0.74) or PAC (50% vs. 87%, P = 0.68).
Conclusion
: Primary resistance to metronidazole influences the H. pylori cure rate of anti‐H. pylori proton pump inhibitor‐based triple therapies which include this antibiotic. A similar trend exists for primary clarithromycin resistance.
Abstract Background The natural history of Barrett's Oeosphagus is not completely clarified and Barrett's Oeosphagus Registries are considered useful tools to expand our knowledge on this disease. A ...Barrett's Oeosphagus Registry has been therefore established in the Veneto Region and neighbouring provinces. Aims The aims of the Registry are to assess the demographical, endoscopical and histological characteristics of Barrett's Oeosphagus patients; the prevalence of non-invasive neoplasia and Barrett's Adenocarcinoma and the timing and incidence of Barrett's Oeosphagus progression to malignancy. Methods An interdisciplinary committee of endoscopists, pathologists and information technology experts was established in 2004 to design a website-based Barrett's Oesophagus Registry for the Veneto Region and neighbouring north-eastern Italian provinces. Protocols for endoscopies and biopsies and standard reports were carefully defined. Results In the first 18 months, 397 patients with endoscopically visible and histologically proven Barrett's Oeosphagus were enrolled in the Registry; the median age of these patients was 66 years (male:female = 3:1). Most patients (75%) had a Short Segment of Barrett's Oesophagus (≤3 cm) and only 1 in 4 had a Long Segment of Barrett's Oesophagus (>3 cm). Long Segment of Barrett's Oesophagus patients were 5 years older than the Short Segment of Barrett's Oesophagus patients ( p < 0.05), suggesting a progression from Short Segment of Barrett's Oesophagus to Long Segment of Barrett's Oesophagus. Though no data are available on the incidence of non-invasive neoplasia or Barrett's Adenocarcinoma (i.e. , progression to cancer at least 12 months after enrolment), the prevalence of neoplastic lesions (found within 12 months of enrolment) was 5% for Short Segment of Barrett's Oesophagus and 19% for Long Segment of Barrett's Oesophagus, indicating that a careful multiple-biopsy endoscopic protocol is needed, especially when Long Segment of Barrett's Oesophagus are suspected at endoscopy. The prevalence of Barrett's Adenocarcinoma among patients with non-invasive neoplasia was 1/17 cases of low-grade non-invasive neoplasia and 2/3 cases of high-grade non-invasive neoplasia, indicating that these patients require strict endoscopic and bioptic follow-up. Conclusion A regional Barrett's Oeosphagus Registry is feasible at a relatively low cost and enables significant data to be collected in a relatively short time. The use of a standardised endoscopic nomenclature and report form, a strict biopsy protocol, a standard report for pathologists improves the quality of endoscopic and histological diagnoses.
Summary
Background : Whether liver steatosis affects sustained virological response in patients with chronic hepatitis C is still under discussion.
Aim : To evaluate the impact of liver steatosis in ...patients treated (for chronic hepatitis C) with combination therapy.
Methods : We evaluated 97 (male/female 82/15, mean age 41.1 years) consecutive naïve patients treated with pegylated interferon alpha‐2b plus ribavirin.
Results : Prevalence and severity of liver steatosis were significantly associated with genotype 3a grade 3–4 in 14 of 32 patients (44%) vs. 8 of 65 patients (12%) with other genotypes; P = 0.001, while steatosis grade 1 (<10% of hepatocytes affected) was more frequently associated with genotype 1a/1b 9/39 (23%) vs. 4/57 (7%); P = 0.02. Overall, sustained virological response was 62.8%, and was statistically uninfluenced by the presence/absence of liver steatosis. On the contrary, the following variables were independently associated with sustained virological response at logistic regression analysis: genotype other than 1a/1b, positive association, (odds ratio 3.4, P < 0.04), and low‐grade liver steatosis, negative association, (odds ratio 9.0, P =0.009), whereas sustained virological response was unaffected by severe liver steatosis, which was mainly associated with genotypes 2 and 3 steatosis grade 2, 18/29 (62%); grade 3, 10/12 (83%); grade 4, 7/10 (70%).
Conclusions : Only low‐grade liver steatosis negatively affects the outcome of combination therapy, with peginterferon alpha‐2b plus ribavirin, while severe steatosis (which is virus‐related in most cases) has no impact on virological response.
Background:
Advancing age may influence clarithromycin’s pharmacokinetics. No studies have yet compared the effects of different dosages of clarithromycin in combination with a proton pump inhibitor ...and amoxicillin in elderly patients.
Aim:
To compare the efficacy and tolerability of clarithromycin 250 mg vs. clarithromycin 500 mg twice daily (b.d.) in combination with pantoprazole and amoxicillin in elderly patients.
Methods:
One hundred and fifty‐four elderly patients with H. pylori‐associated ulcer disease or chronic gastritis were consecutively randomized to receive pantoprazole 40 mg daily plus amoxicillin 1 g, and either clarithromycin 250 mg b.d. (PAC 250) or clarithromycin 500 mg b.d. (PAC 500). Two months after therapy, endoscopy and gastric biopsies were repeated.
Results:
The cure rates of H. pylori infection in the PAC 250 and PAC 500 groups were, respectively, 83% and 79% (ITT analysis) and 94% and 88% (PP analysis) (P=N.S.). Significant decreases in chronic gastritis activity both in the body (P < 0.00001) and the antrum (P < 0.0001) of the stomach were found in H. pylori‐cured patients, independently of clarithromycin dosage. Four patients in PAC 250 (5%) and seven in PAC 500 (9%) reported adverse events (P=N.S.). One patient in PAC 250 (25%) and three in PAC 500 (43%) discontinued the study because of these drug‐related side‐effects (P=N.S.).
Conclusions:
In elderly patients, 1‐week triple therapy with a proton pump inhibitor, amoxicillin and clarithromycin is a highly effective and well tolerated anti‐H. pylori treatment. With this combination, clarithromycin at the lower dose of 250 mg b.d. achieved excel‐ lent cure rates and minimized adverse events and costs.
Specific data on anti-H. pylori treatments in elderly people are very scarce. The aim of the study was to evaluate in the elderly the efficacy of different anti-H. pylori therapies and the behaviour ...of serum anti-H. pylori antibodies, pepsinogen A and C, and PGA/PGC ratio induced by the anti-H. pylori treatment.
One hundred and twenty-one dyspeptic patients aged > 60 years (mean age, 73 years; range, 61-89 years) with H. pylori-positive gastric ulcers (17 patients), duodenal ulcers (33 patients) or chronic gastritis (71 patients) were treated with one of the following anti-H. pylori treatments: (A) omeprazole 20 mg/day plus azithromycin 500 mg/day for 3 days; (B) omeprazole 20 mg/day plus azithromycin 500 mg/day for 3 days plus metronidazole 250 mg q.d.s. for 7 days; (C) omeprazole 40 mg/day plus azithromycin 500 mg/day for 3 days plus metronidazole 250 q.d.s. for 7 days; (D) omeprazole 20 mg/day plus clarithromycin 250 b.d. for 7 days; (E) omeprazole 20 mg/day plus clarithromycin 250 b.d. for 7 days plus metronidazole 250 q.d.s. for 7 days; and (F) omeprazole 40 mg/day plus clarithromycin 250 mg b.d. for 7 days plus metronidazole 250 mg q.d.s. for 7 days. At the baseline and 2 months after therapy, endoscopy and serum anti-H. pylori antibodies, pepsinogen A and C, and PGA/PGC ratio were measured.
Ten patients (8.2%) dropped out of the study. Six patients (4.9%) reported side-effects. The eradication rates of the six regimens, expressed using intention-to-treat and per protocol analysis, were, respectively: (A) 39% and 44%; (B) 50% and 56%; (C) 65% and 77%; (D) 47% and 50%; (E) 85% and 90%; and (F) 83% and 87%. The triple therapy for regimens E and F was significantly more effective than dual therapies (regimens A and D; intention-to-treat = P < 0.007, per protocol = P < 0.001) or the triple therapy for regimens B and C (intention-to-treat = P < 0.009, per protocol = P < 0.03). Patients cured of H. pylori infection showed a significant decrease in the activity of gastritis (P < 0.0001), a significant drop in IgG anti-H. pylori (P = 0.0004) and pepsinogen C (P < 0.0001), and an increase in PGA/PGC ratio (P < 0.001), while patients remaining H. pylori-positive showed no changes in the serum parameters.
In the elderly, triple therapy with omeprazole+metronidazole+clarithromycin for 1 week is well tolerated and highly effective; anti-H. pylori antibody and PGC serum levels decrease soon after anti-H. pylori therapy only in patients cured of H. pylori infection.
Background:
The relationship between serum parameters of gastric function and Helicobacter pylori infection in human immunodeficiency virus (HIV)‐positive patients is almost unknown.
Aims:
To ...investigate in HIV‐infected patients: (i) the relationship between serum gastrin and serum pepsinogens over the progressive phases of HIV‐related disease; (ii) the impact of H. pylori infection on gastrin and pepsinogen serum levels and its relation to antral histology; (iii) the prevalence of parietal cell autoantibodies.
Methods:
Fifty‐nine HIV‐positive patients were studied by upper endoscopy plus gastric antral biopsy. Serum samples were tested for gastrin, pepsinogen A, pepsinogen C and parietal cell autoantibodies.
Results:
In patients without overt acquired immunodeficiency syndrome (AIDS), or with a CD4+ count of > 100 × 106 cells/L, mean serum levels of gastrin and pepsinogen C were higher than in subjects with AIDS or with a CD4+ count of < 100 × 106 cells/L (P < 0.01). Only one patient was found to be positive for parietal cell autoantibodies. H. pylori infection was associated with increased values of gastrin and pepsinogen C only in HIV‐positive patients without AIDS or with a CD4+ count of > 100 × 106 cells/L. Atrophy was more frequent in patients with overt AIDS than in those without overt AIDS (57% vs. 33%, P=N.S.), and/or in patients with a CD4+ count of < 100 × 106 cells/L than in those with a CD4+ count of > 100 × 106 cells/L (62% vs. 26%, P < 0.05).
Conclusions:
HIV‐positive patients without overt AIDS have increased serum levels of gastrin and pepsinogen C compared with HIV‐positive patients with overt AIDS.
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