Alimentary Pharmacology & Therapeutics

Gisbert, J. P.; Pajares, J. M.

doi: 10.1111/j.1365-2036.2005.02418.xpmid: 15801914

Summary Aims : To systematically review the efficacy on ulcer healing of 1‐week combination of a proton pump inhibitor plus two antibiotics and to perform a meta‐analysis of randomized clinical trials to evaluate whether 7 days of proton pump inhibitor‐based triple therapy is sufficient to heal peptic ulcer. Methods : Studies where 1‐week proton pump inhibitor‐based triple therapy was administered to heal peptic ulcer were included. Randomized clinical trials comparing the efficacy on ulcer healing of 7‐day proton pump inhibitor‐based triple therapy versus this same regimen but prolonging the proton pump inhibitor for several more weeks were included in the meta‐analysis. Electronic and manual bibliographical searches were conducted. Meta‐analysis was performed combining the odds ratios of the individual studies. Results : Twenty‐four studies (2342 patients) assessed ulcer healing with 1‐week proton pump inhibitor‐based triple therapy. Mean healing rate was 86%, and 95% in Helicobacter pylori‐eradicated patients. Six studies (862 patients), were included in the meta‐analysis. Mean ulcer healing rate with a 7‐day treatment was 91% versus 92% when proton pump inhibitor was prolonged for 2–4 more weeks (odds ratio = 1.11; 95% confidence interval = 0.71–1.74). Conclusion : In patients with peptic ulcer and H. pylori infection, prolonging therapy with proton pump inhibitor after a triple therapy for 7 days with a proton pump inhibitor and two antibiotics is not necessary to induce ulcer healing.

Bour, B.; Staub, J.‐L.; Chousterman, M.; Labayle, D.; Nalet, B.; Nouel, O.; Pariente, A.; Tocque, E.; Bonnot‐Marlier, S.

doi: 10.1111/j.1365-2036.2005.02413.xpmid: 15801915

Summary Background : On‐demand treatment may be an alternative in the long‐term treatment of non‐severe gastro‐oesophageal reflux disease in patients with frequent symptomatic relapses. Aim : To compare the efficacy of on‐demand treatment with rabeprazole 10 mg versus continuous treatment in the long‐term treatment of patients with frequent symptomatic relapses of mild to moderate gastro‐oesophageal reflux disease. Methods : This randomized, open‐label study enrolled patients diagnosed with non‐erosive reflux disease or oesophagitis grade 1 or 2 (Savary–Miller classification) reporting frequent symptomatic relapses (requiring ≥2 courses of antisecretory therapy during the previous year), whose intensity is rated at least moderate (>2 on a 5‐point Likert scale). After a 4‐week selection phase with rabeprazole 10 mg once daily, patients reporting symptom relief (Likert score ≤2) were randomized to receive either rabeprazole 10 mg continuous treatment or on‐demand treatment for 6 months. The main evaluation criterion was the rate of symptom relief (scored on the Likert scale) after 6 months. Results : One hundred and seventy‐six patients were enrolled in the 4‐week selection phase (men, 53%; mean age, 49 years; non‐erosive reflux disease, 36.4%; gastro‐oesophageal reflux disease 1, 53.4%; gastro‐oesophageal reflux disease 2, 10.2%). Rabeprazole relieved symptoms in 88.6% of patients. Of this group, 152 were randomized to the comparative phase to receive rabeprazole 10 mg continuous treatment (once daily) or on‐demand treatment (continuous treatment, n = 81; on‐demand treatment, n = 71). At month 6 (end point), the symptom relief rate was slightly higher for patients in the continuous treatment group compared with those in the on‐demand treatment group: 86.4% versus 74.6%, respectively. This difference was not statistically significant (P = 0.065). For the overall quality of life score, there was no difference between the continuous treatment and on‐demand treatment groups (86.25 and 84.94). Mean daily consumption of rabeprazole was significantly lower in the on‐demand treatment group versus the continuous treatment group (0.31 tablets versus 0.96 tablets; P < 0.0001). Conclusion : On‐demand therapy with rabeprazole 10 mg provides an alternative to continuous therapy in patients with mild to moderate gastro‐oesophageal reflux disease suffering from frequent symptomatic relapses.

Schmidt, N.; Peitz, U.; Lippert, H.; Malfertheiner, P.

doi: 10.1111/j.1365-2036.2005.02425.xpmid: 15801916

Summary Background : Dyspepsia is common in gastric cancer, but also in many benign conditions. European Helicobacter pylori Study Group and American Gastroenterological Association guidelines recommend endoscopy in dyspepsia for patients with alarm symptoms or at age >45 years. However, recommendations are controversial. Aim : To investigate whether criteria for endoscopy in patients with dyspepsia are adequate to detect gastric cancer. Methods : In 215 patients at initial diagnosis of gastric adenocarcinoma, symptoms were classified as alarm and non‐alarm. Cases were staged according to the TNM system. Stages T1–T3NxM0 were defined as potentially curable. Results : Dyspepsia was present in 128 patients. Among patients with dyspepsia, 15 were ≤45 years and 41 denied alarm symptoms. The combination of both criteria excluded only three (2.3%) patients from endoscopy, but increasing the threshold to >50 and >55 years would have raised the rate of excluded patients to seven (5.5%) and 11 (8.6%). Only 53 potentially curable stages and 18 early gastric cancers occurred, but the tumour stage was not associated with dyspepsia duration, age threshold of 45 years, or alarm symptoms. Conclusions : Our results support current European Helicobacter Study Group and American Gastroenterological Association criteria for endoscopy in patients with dyspepsia to detect gastric cancer. Regardless, most cancers are advanced at detection.

Mohammed, I.; Nightingale, P.; Trudgill, N. J.

doi: 10.1111/j.1365-2036.2005.02426.xpmid: 15801917

Summary Aim: To examine the prevalence of gastro‐oesophageal reflux disease symptoms and potential risk factors among community subjects. Methods: A questionnaire was sent to 4000 subjects, stratified by age, gender and ethnicity to be representative of the local population. Gastro‐oesophageal reflux disease symptoms were defined as at least weekly heartburn or acid regurgitation. Results: 2231 responded (59%), 691 refused to participate and seven were incomplete. 1533 (41%) were evaluable (637 male, mean age 51 years, range: 20–80). The prevalence of gastro‐oesophageal reflux disease symptoms was 21%. Smoking, excess alcohol, irritable bowel syndrome, increasing body mass index, a family history of upper gastrointestinal disease, increasing Townsend deprivation index, anticholinergic drugs (all P < 0.0001), weight gain, antidepressant drugs, inhaled bronchodilators, no educational attainment (all P < 0.01), south Asian origin (P = 0.02) and manual work (P < 0.05) were associated with gastro‐oesophageal reflux disease symptoms. Multivariate logistic regression revealed increasing body mass index, a family history of upper gastrointestinal disease, irritable bowel syndrome, south Asian origin (all P < 0.0001), smoking, excess alcohol, no educational attainment and anticholinergic drugs (all P < 0.01) were independently associated with gastro‐oesophageal reflux disease symptoms. Conclusions: Frequent gastro‐oesophageal reflux disease symptoms affect 21% of the population. Increasing body mass index, a family history of upper gastrointestinal disease, irritable bowel syndrome, south Asian origin, smoking, excess alcohol, social deprivation and anticholinergic drugs are independently associated with gastro‐oesophageal reflux disease symptoms.

Roblin, X.; Serre‐Debeauvais, F.; Phelip, J.‐M.; Faucheron, J.‐L.; Hardy, G.; Chartier, A.; Helluwaert, F.; Bessard, G.; Bonaz, B.

doi: 10.1111/j.1365-2036.2005.02419.xpmid: 15801918

Summary Background : 6‐Thioguanine (6‐tioguanine) nucleotides are the active metabolites of azathioprine. Aim : The aim of the study was to evaluate the rate of clinical remission without steroids in steroid‐dependent Crohn's disease and ulcerative colitis patients receiving azathioprine, the medium‐ and long‐term efficacy and the predictive factors of clinical response when monitoring 6‐tioguanine. Methods : Steroid‐dependent Crohn's disease and ulcerative colitis patients receiving either azathioprine or not (treated later with a daily dose of 2.5 mg/kg) were prospectively included. 6‐Tioguanine was monitored at 1 and 2 months and every 3 months thereafter for 1 year. The azathioprine dose was adapted to reach a 6‐tioguanine level of >250 pmol/8 × 108 red blood cells. Thiopurine methyltransferase genotype/phenotype was evaluated in some patients. Results : A total of 106 patients were prospectively included (70 Crohn's disease, 36 ulcerative colitis). The clinical remission rate without steroids in patients receiving azathioprine, in intention‐to‐treat analysis, was 72% and 59% at 6 and 12 months, respectively. The remission rate was significantly higher in patients with 6‐tioguanine >250 pmol/8 × 108 RBC (86% and 69% at 6 and 12 months, respectively; P < 0.01). No significant difference was observed between Crohn's disease and ulcerative colitis patients whether treated by azathioprine or not on inclusion. In the univariate analysis, the absence of Crohn's disease stenosis, a 6‐tioguanine level >250 pmol/8 × 108 RBC, and an increase of erythrocyte mean corpuscular volume were the factors predictive of a favourable clinical response. In the multivariate analysis, only a 6‐tioguanine level of >250 pmol/8 × 108 red blood cells was a predictive factor of favourable clinical remission. Conclusions : Clinical remission without steroids is significantly more likely when monitoring 6‐tioguanine so as to reach a level of >250 pmol/8 × 108 red blood cells in steroid‐dependent Crohn's disease and ulcerative colitis patients receiving azathioprine (86% and 69% at 6 and 12 months, respectively).

Yuen, M.‐F.; Chow, D. H.‐F.; Tsui, K.; Wong, B. C.‐Y.; Yuen, J. C.‐H.; Wong, D. K.‐H.; Lai, C.‐L.

doi: 10.1111/j.1365-2036.2005.02410.xpmid: 15801919

Summary Background : Long‐term effect of YMDD mutations on liver histology in Chinese hepatitis B patients is unknown. Aim : To examine the effect of prolonged lamivudine treatment on liver histology in Chinese patients with and without YMDD mutations. Methods : Liver histology was assessed in 85 patients on long‐term lamivudine at baseline and year 1, and at year 3 for 25 patients. Results : Comparing patients with and without YMDD mutations at year 1, the former had higher baseline median necroinflammatory (11 vs. six respectively, P = 0.014) and fibrosis scores (three vs. one respectively, P = 0.001). The proportion of patients with improvement in necroinflammation and worsening of fibrosis was comparable for patients with and without YMDD mutations at year 1 (57.1%, 14.3% vs. 55%, 15% respectively) and year 3 (57.9%, 26.3% vs. 50%, 16.7% respectively). Comparing the histology at year 1 and 3, more patients with YMDD mutations developing after year 1 had worsening of necroinflammation than patients with persistent YMDD wild type (53.8% vs. 25% respectively). Conclusions : Patients who developed YMDD mutations had higher baseline histological scores. With YMDD mutations, the liver histology became less favourable after 3 years than at the first year, although there was still improvement when compared with that at baseline.

Koeda, N.; Iwai, M.; Kato, A.; Suzuki, K.

doi: 10.1111/j.1365-2036.2005.02409.xpmid: 15801920

Summary Background : No definitive method for quantitative evaluation of hepatic function has as yet been established. Aim : To investigate whether the 13C‐phenylalanine breath test would be useful for the evaluation of hepatic function in patients with liver cirrhosis and acute hepatitis. Methods : l‐(1‐13C)‐phenylalanine was administered orally in a dose of 100 mg to 25 patients with liver cirrhosis, 22 patients with acute hepatitis and 10 healthy subjects. The relationships of the cumulative excretion with the 13C‐%dose/h, blood biochemical parameters and asialoscintigraphy were investigated. Results : In liver cirrhosis patients, the cumulative excretion showed correlations with hepatic function tests, asialoscintigraphy, clinical stage and portal hypertension. In acute hepatitis patients, the cumulative excretion showed correlations with hepatic function tests. There were positive correlations between the cumulative excretion and the 13C‐%dose/h at 20 min (Phe20) and 13C‐%dose/h at 30 min (Phe30) in liver cirrhosis and acute hepatitis patients. Multiple regression analysis demonstrated that total bilirubin, total cholesterol and absence of varices were independent determinants of cumulative excretion in liver cirrhosis patients and prothrombin time in acute hepatitis patients. Conclusion : The 13C‐phenylalanine breath test may allow hepatic function to be evaluated non‐invasively in liver cirrhosis and acute hepatitis patients, and the Phe20 and Phe30 may be useful for determination of function at a single time‐point.

Fabrizi, F.; De Vecchi, A. F.; Como, G.; Lunghi, G.; Martin, P.

doi: 10.1111/j.1365-2036.2005.02416.xpmid: 15801921

Summary Background : Dialysis patients remain a high‐risk group for hepatitis C virus infection. The current diagnosis of hepatitis C virus in dialysis patients includes serological measurement of anti‐hepatitis C virus antibody; however, nucleic acid amplification technology for assessing hepatitis C virus viraemia is commonly used in other populations. An enzyme‐linked immunosorbent assay test for detecting antibody to hepatitis C nucleocapsid core antigen (hepatitis C virus core antigen) in human serum has been recently developed (hepatitis C virus Core Antigen enzyme‐linked immunosorbent assay test). It is conceived for screening of donor blood products to significantly reduce the ‘serologic window’ occurring before seroconversion during acute hepatitis C virus. Aim and methods : A cohort (n = 72) of patients on maintenance haemodialysis in a single unit in the years 2000–2003 was included. Study patients were tested monthly by hepatitis C virus Core Antigen enzyme‐linked immunosorbent assay in a prospective, clinical trial. Routine results obtained by hepatitis C virus Core Antigen enzyme‐linked immunosorbent assay test were confirmed by assessing hepatitis C virus viraemia by branched‐chain DNA (bDNA) signal amplification assay. Results : De novo hepatitis C virus infection was identified in three patients during the study period; the hepatitis C virus incidence was 1.38% (95% confidence intervals, 1.31–4.09) per year. In each patient, hepatitis C virus core antigen testing allowed the serological identification of acute hepatitis C virus before anti‐hepatitis C virus seroconversion. Hepatitis C virus RNA testing confirmed the results obtained by hepatitis C virus Core Antigen enzyme‐linked immunosorbent assay in all cases. The time from initial hepatitis C virus detection by hepatitis C virus Core Antigen Assay and anti‐hepatitis C virus seroconversion was not greater than four weeks. Two (67%) of three patients with de novo hepatitis C virus acquisition were HBsAg negative; both these patients underwent an initial phase of hepatitis C virus viraemia that was associated with an increase in alanine aminotransferase activity and preceded the seroconversion to anti‐hepatitis C virus antibody. Nosocomial transmission of hepatitis C virus between haemodialysis patients was implicated in at least two (67%) of these three patients. Conclusions : Serological testing for hepatitis C virus core antigen can identify acute hepatitis C virus infection before anti‐hepatitis C virus seroconversion. The time from initial hepatitis C virus detection by hepatitis C virus core antigen assay and anti‐hepatitis C virus seroconversion was not >4 weeks. De novo acquisition of hepatitis C virus in haemodialysis was associated with a rise in alanine aminotransferase levels. Hepatitis C virus core antigen enzyme‐linked immunosorbent assay test results can be obtained in routine laboratories without the need of special equipment or training. Hepatitis C virus core antigen testing among anti‐hepatitis C virus negative patients on maintenance dialysis is suggested in order to early assess de novo hepatitis C virus within dialysis units.

Schwimmer, J. B.; Middleton, M. S.; Deutsch, R.; Lavine, J. E.

doi: 10.1111/j.1365-2036.2005.02420.xpmid: 15801922

Summary Background : Children with non‐alcoholic steatohepatitis are insulin‐resistant and metformin has been proposed as a potential therapy. However, paediatric safety and efficacy data are absent. Aim : To test the hypothesis that metformin therapy will safely improve markers of liver disease in paediatric non‐alcoholic steatohepatitis. Methods : Single‐arm open‐label pilot study of metformin 500 mg twice daily for 24 weeks in non‐diabetic children with biopsy‐proven non‐alcoholic steatohepatitis. Results : Ten obese children (mean body mass index 30.4) enrolled and completed the trial. Mean alanine aminotransferase and aspartate aminotransferase (AST) improved significantly (P < 0.01) from baseline (184, 114 U/L) to end of treatment (98, 68 U/L). Alanine aminotransferase normalized in 40% and AST normalized in 50% of subjects. Children demonstrated significant improvements in liver fat measured by magnetic resonance spectroscopy (30–23%, P < 0.01); insulin sensitivity measured by quantitative insulin sensitivity check index (0.294–0.310, P < 0.05); and quality of life measured by pediatric quality of life inventory 4.0 (69–81, P < 0.01). Conclusion : Open‐label treatment with metformin for 24 weeks was notable for improvement in liver chemistry, liver fat, insulin sensitivity and quality of life. A large randomized‐controlled trial is needed to definitively determine the efficacy of metformin for paediatric non‐alcoholic steatohepatitis.

Granito, A.; Zauli, D.; Muratori, P.; Muratori, L.; Grassi, A.; Bortolotti, R.; Petrolini, N.; Veronesi, L.; Gionchetti, P.; Bianchi, F. B.; Volta, U.

doi: 10.1111/j.1365-2036.2005.02417.xpmid: