Aliment Pharmacol Ther

Review article: glycyrrhizin as a potential treatment for chronic hepatitis C.

Year 1998
van Rossum TG. Vulto AG. de Man RA. Brouwer JT. Schalm SW.
Department of Hepatogastroenterology, Erasmus University Hospital, Rotterdam, The Netherlands.
Chronic hepatitis C is a slowly progressive liver disease that may evolve into cirrhosis with its potential complications of liver failure or hepatocellular carcinoma. Current therapy with alpha-interferon is directed at viral clearance, but sustained response is only achieved in 20-40% of patients without cirrhosis, and less than 20% in patients with cirrhosis who have the greatest need for therapy. Treatment for those who do not respond to anti-viral therapy is highly desirable. In Japan glycyrrhizin has been used for more than 20 years as treatment for chronic hepatitis. In randomized controlled trials, glycyrrhizin induced a significant reduction of serum aminotransferases and an improvement in liver histology compared to placebo. Recently, these short-term effects have been amplified by a well-conducted retrospective study suggesting that long-term usage of glycyrrhizin prevents development of hepatocellular carcinoma in chronic hepatitis C. The mechanism by which glycyrrhizin improves liver biochemistry and histology are undefined. Metabolism, pharmacokinetics, side-effects, and anti-viral and hepatoprotective effects of glycyrrhizin are discussed.

Antibiotic prophylaxis for ERCP: a comparison of oral ciprofloxacin with intravenous cephazolin in the prophylaxis of high-risk patients.

Year 1998
Davis AJ. Kolios G. Alveyn CG. Robertson DA.
Department of Gastroenterology, Royal United Hospital, Bath, UK.
BACKGROUND: Cholangitis and septicaemia are serious complications of endoscopic retrograde cholangiopancreatography (ERCP). They occur mainly following therapeutic ERCP in the setting of an obstructed biliary system. The optimum prophylactic antibiotic regimen in such patients is not yet defined but usually depends on intravenous agents. AIM: To compare the efficacy of oral ciprofloxacin with intravenous cephazolin. METHODS: One hundred and fifty patients at high risk from septic complications were randomized prospectively to either oral ciprofloxacin (750 mg b.d.) or intravenous cephazolin (1 g b.d.), commenced at least 90 min prior to the ERCP and continued for 3 days. Bacteriological cultures were taken from bile during the procedure and from blood both immediately and at 24 h post-procedure. RESULTS: There were no significant differences between the two treatment groups in the pre-ERCP clinical or radiological findings or in the types of procedure performed. One patient did not undergo an ERCP and was excluded from the final analysis. Of the 77 patients in the ciprofloxacin group there were no positive blood cultures and one positive culture from a nasobiliary drain. Two out of the 72 cephazolin patients had positive blood cultures immediately post-ERCP; one of these two patients and one other cephazolin patient had positive bile cultures. There were no cases of cholangitis or septicaemia in the ciprofloxacin group and three cases in the cephazolin group. One patient from each treatment group died within the 7-day study. Adverse drug reactions were minimal and none of the different clinical outcomes in the two groups reached statistical significance. CONCLUSION: Oral ciprofloxacin is a cost-effective prophylactic agent for high-risk ERCP.

The effect of rectally administered steroids on bone turnover: a comparative study.

Year 1998
Robinson RJ. Iqbal SJ. Wolfe R. Patel K. Abrams K. Mayberry JF.
Gastrointestinal Research Unit, Leicester General Hospital, UK.
BACKGROUND: Oral glucocorticoids contribute significantly to the risk of osteoporosis in patients with inflammatory bowel disease. Less well established are the effects of rectally administered steroids on bone metabolism. AIM: To investigate the effects of two widely used rectal foam preparations (prednisolone metasulphobenzoate and hydrocortisone acetate) on biochemical markers of bone turnover. METHODS: Twenty-four patients with active inflammatory bowel disease randomly received a standard course of either prednisolone metasulphobenzoate or hydrocortisone acetate for 2 weeks. Biochemical markers of bone turnover were measured before, during and after treatment. Bone formation markers measured were serum osteocalcin (BGP) and bone-specific alkaline phosphatase (BALP). Urinary deoxypyridinoline (DPD) was measured to assess bone resorption. RESULTS: Disease activity scores improved during treatment (difference in mean Powell-Tuck score = 3.4, 95% CI: 2.0-4.8, P < 0.0001) and were similar in both hydrocortisone and prednisolone-treated groups. There was no significant reduction in BALP or BGP during treatment with either steroid preparation, and urinary DPD did not change significantly during treatment. CONCLUSIONS: During a 2-week course of rectal hydrocortisone acetate or prednisolone metasulphobenzoate, there was no significant change in biochemical markers of bone formation or resorption. These results suggest that pharmacological doses of rectal steroid foam preparations do not significantly impair bone turnover in patients with inflammatory bowel disease.

Meta-analysis of somatostatin, octreotide and gabexate mesilate in the therapy of acute pancreatitis.

Year 1998
Andriulli A. Leandro G. Clemente R. Festa V. Caruso N. Annese V. Lezzi G. Lichino E. Bruno F. Perri F.
Division of Gastroenterology, Ospedale Casa Sollievo della Sofferenza, IRCCS, San Giovanni Rotondo, Italy.
BACKGROUND: Autodigestion of the pancreas, secondary to the activation of digestive enzymes, is the pathogenetic mechanism of acute pancreatitis (AP). AIM: Clinical trials in which somatostatin (SS), octreotide (OCT) and gabexate mesilate (FOY) were used to treat patients with AP, were submitted to a meta-analytical evaluation. Five end-points were evaluated: early and overall mortality, patients with complications, complication rate, and patients who needed surgery. RESULTS: In mild AP, no agent proved of value. In severe AP, both SS and OCT were beneficial in improving the overall mortality: the odds ratios (OR) were, respectively, 0.36 (95% CI: 0.20-0.64, P = 0.001) and 0.57 (95% CI: 0.35-0.88, P = 0.006). FOY had no effect on either early or overall mortality, but was effective in improving complication rate (OR = 0.70, 95% CI: 0.56-0.88, P = 0.02), number of patients with complications (OR = 0.61, 95% CI: 0.41-0.91, P = 0.01), and number of cases submitted to surgery (OR = 0.60, 95% CI: 0.39-0.92, P = 0.01). SS and OCT had no effect on these latter outcomes. CONCLUSIONS: Antisecretory agents, such as SS and OCT, are able to reduce mortality without affecting complications, whereas antiproteases, such as FOY, have no effect on mortality but do reduce complications. A trial exploring the efficacy of combining antisecretory agents with antiproteases would be of great benefit in patients with severe AP.

Changes in Helicobacter pylori-induced gastritis in the antrum and corpus during 12 months of treatment with omeprazole and lansoprazole in patients with gastro-oesophageal reflux disease.

Year 1998
Stolte M. Meining A. Schmitz JM. Alexandridis T. Seifert E.
Institut fur Pathologie, Klinikum Bayreuth, Germany.
BACKGROUND: Several studies have shown that treatment with omeprazole leads to aggravation of Helicobacter pylori gastritis in the corpus. Whether this also applies to lansoprazole, and whether, in comparison with omeprazole, there are differences in therapy-induced gastritis parameter changes remains unclear. METHODS: In 111 patients infected with H. pylori and with gastro-oesophageal reflux disease we investigated the gastritis parameters in antral and corpus mucosa before and after 2, 6 and 12 months of treatment with 15 or 30 mg lansoprazole or 20 mg omeprazole/day. RESULTS: In all groups the different treatments had a similar effect: in both regions of the stomach, suppression or partial elimination of H. pylori was seen. However, improvement in the inflammation was observed only in the antrum, while in the corpus most gastritis parameters worsened significantly. There was no increase in intestinal metaplasia or atrophy. CONCLUSION: In common with omeprazole, lansoprazole aggravates the gastritis parameters in the corpus but improves them in the antrum. Treatment with proton pump inhibitors does not result in any increase in the incidence of atrophy/intestinal metaplasia. However, as gastritis predominating in the corpus seems to be associated with an elevated carcinogenic risk, consideration should be given to prophylactic H. pylori eradication therapy before initiating proton pump inhibitor treatment.

The management of acid-related dyspepsia in general practice: a comparison of an omeprazole versus an antacid-alginate/ranitidine management strategy. Compete Research Group [corrected]

Year 1998
Mason I. Millar LJ. Sheikh RR. Evans WM. Todd PL. Turbitt ML. Taylor MD.
The Surgery, The Old Orchard, Limekilns, Fife, UK.
BACKGROUND: There is need for an evidence-based comparison of clinical management strategies to provide the rationale for selection of a particular therapeutic approach to treatment. Ideal dyspepsia treatment should quickly and conveniently alleviate patient symptoms whilst also minimizing the use of healthcare resources. AIM: To examine dyspepsia symptom relief over 16 weeks and compare an omeprazole clinical management strategy with a commonly used combination of antacid-alginate followed by H2-antagonist. METHODS: Seven hundred and twenty-five patients participated in this randomized, open, parallel group comparison over 16 weeks. Patients were randomized to receive either an omeprazole treatment strategy (363) consisting of omeprazole 10 mg stepping up to 20 mg and 40 mg as required, or an antacid-alginate/ranitidine treatment strategy (362) consisting of antacid-alginate 10 mL q.d.s. stepping up to ranitidine 150 mg b.d. and 150 mg q.d.s. as required. RESULTS: A greater proportion of patients receiving the omeprazole clinical management strategy had achieved the stringent health target of complete symptom relief (61 vs. 40%, P < 0.0001) at 16 weeks. Forty-six per cent of omeprazole-treated patients were symptom free after the first 10 mg step compared to only 17% in the antacid-alginate treated group (P = 0.0001). Total relief of heartburn, the most common symptom at entry, was achieved by more patients in the omeprazole treatment group than the antacid-alginate/ranitidine treatment group, 62 vs. 36%, respectively, at 4 weeks, and 81 vs. 60% at 16 weeks (P = 0.0001). CONCLUSION: Treatment with the omeprazole clinical management strategy was superior to the antacid-alginate/ranitidine management strategy in providing relief of acid-related dyspepsia symptoms after 16 weeks. In addition, the omeprazole treatment strategy involved fewer GP consultations and thus minimized the use of other healthcare resources.

Lansoprazole triple therapy for Helicobacter pylori--is 5 days enough?

Year 1998
O'Connor HJ. McLoughlin R. Kelly S. Laundon J. Cunnane K.
Department of Medicine, General Hospital, Tullamore, Co. Offaly, Ireland.
BACKGROUND: Seven-day proton pump inhibitor triple therapy is currently the treatment of choice for Helicobacter pylori infection. It is unclear whether triple therapy for less than 7 days might preserve efficacy while at the same time improving patient acceptability and compliance. AIM: To evaluate the Helicobactericidal efficacy, ulcer healing capacity and patient acceptability of a 5-day lansoprazole-based triple therapy regimen. METHODS: Sixty-nine consecutive patients with H. pylori-positive peptic ulcer received lansoprazole 30 mg twice daily in combination with metronidazole 400 mg twice daily and clarithromycin 250 mg twice daily for 5 days. Ulcer healing medication was not continued after the 5-day regimen. H. pylori status was assessed before and at least 4 weeks after therapy by rapid urease test and histology. Adverse events and compliance were assessed by direct questioning. RESULTS: All 69 patients attended for repeat endoscopy and 63 were H. pylori-negative after therapy giving a cure rate of 91%, (95%, Cl: 85-98%). Of the 59 patients with active ulcers, 58 were healed at repeat endoscopy giving an ulcer healing rate of 98% (95% Cl: 92-100%). All patients fully complied with therapy and mild adverse events, mainly gastrointestinal, were reported by 11 patients (16%). CONCLUSIONS: Five-day lansoprazole triple therapy is an effective regimen for H. pylori infection which combines a high cure rate and ulcer healing efficacy with the advantages of excellent patient acceptability and compliance.

Bismuth-containing single-antibiotic 1-week triple therapy for Helicobacter pylori eradication.

Year 1998
Scott BB.
Department of Medicine, County Hospital, Lincoln, UK.
BACKGROUND: Although bismuth was both the first drug shown to alter the natural history of peptic ulcer disease and also a constituent of the first very effective eradication regimens, it has been excluded from the newer regimens, despite its safety and low cost, in favour of two antibiotics. AIM: To asses a novel 1-week regimen consisting of bismuth, clarithromycin and a proton pump inhibitor in routine clinical practice. METHODS: One hundred and three consecutive patients with peptic ulcer disease and antral biopsies containing Helicobacter pylori were given a 7-day course of treatment with bismuth (tripotassium dicitrato bismuthate chelate) 120 mg q.d.s., clarithromycin 500 mg t.d.s. and lansoprazole 30 mg o.d. Completeness of eradication was assessed by a l3C-urea breath test, in all except three patients, at least 4 months later. RESULTS: Of the 100 patients who were assessed in this open treatment study 84 (84%; 95% CI: 77-91%) had a negative breath test. Minor side-effects were reported by 14% and more troublesome side-effects (nausea, vomiting, diarrhoea, hallucinations, nasty taste and body pains) were reported by 10%. CONCLUSIONS: A 1-week course of triple therapy including bismuth, clarithromycin and a proton pump inhibitor is effective in routine clinical practice and is well tolerated.