Helicobacter pylori infection: new challenges.
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Publications and source records attributed to R Pellicano.
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Since the latest decade, several studies have reported on the association between chronic Helicobacter pylori (H. pylori) or Helicobacter species (H. species) infection and a variety of extragastric manifestations. These include ischaemic heart disease (IHD), liver diseases, skin diseases, blood disorders and others. However, the hypothesis of an aetiological role has not yet been fully investigated. The epidemiological studies have frequently involved control selection bias, population of small sizes, and presence of confounders, like age and socio-economic conditions. Randomised, long-term and large studies on the follow-up of H. pylori eradication in extragastric diseases are lacking. The present paper attempts to highlight both the epidemiological source of the actual controversies and the biological plausibility for a causal role of H. pylori or H. species infection, in the pathogenesis of some of the most debated extragastric manifestations. Although currently available data do not provide proof of the role of H. pylori infection in the pathogenic mechanism of extragastric diseases, a potential relationship cannot be ruled out. Thus, the need for extensive studies with appropriate epidemiological and clinical approaches is evident.
BACKGROUND: Helicobacter pylori (H. pylori) infection plays an important role in the pathogenesis of duodenal ulcer (DU) disease. Low DU recurrences and reinfection rates were universally described, when treatment was effective. It has been suggested that short-term triple therapy, comprising a proton pump inhibitor plus two antibiotics (clarithromycin, amoxicillin or a nitroimidazole), should be used as first choice in treating H. pylori infection. Nevertheless, conflicting results have been reported on using these treatment regimens in different countries, due to the resistance of H. pylori against one or more antibiotics. Our aim was to compare the efficacy, for H. pylori eradication, of 1-week triple therapy versus 10 and 14-day triple schedules, in patients with a history of recurrent DU. METHODS: A total of 159 patients (85 males, mean age 59.2+/-3.2 years) was randomly treated with a triple therapy including a standard dose of omeprazole twice daily, amoxicillin 1 g twice daily and metronidazole 500 mg twice daily. Fifty-three patients received 1-week triple therapy (Group I), 53 subjects were treated with 10-day triple therapy (Group II) and 53 others with 14-day triple therapy (Group III). H. pylori infection at entry and eradication, at least 4 weeks after therapy had ended, was assessed by 13C urea breath test and histology on biopsies from the antrum and the corpus. RESULTS: Of the 159 subjects randomised into the study, 6 (3 in group II and 3 in group III) were excluded from the per protocol (PP) analysis because of discontinuations. At the end of the course of treatment, the overall H. pylori eradication rate in the intention-to-treat analysis, was 73.5% (39/53) in group I, 71.6% (38/53) in group II and 73.5% (39/53) in group III, without any statistically significant difference. Moreover, the PP analysis also showed no statistical differences, with an eradication rate of 73.5% (39/53) in group I, 76% (38/50) in group II and 78% (39/50) in group III. The reported frequency of side-effects was evenly distributed between the groups, but 6 patients (3.7%) stopped because of adverse events only in groups II and III. CONCLUSIONS: The present study shows that there is no significant difference between the three regimens although the 14-day triple therapy shows a slightly higher H. pylori eradication rate. There is a strong need, in our region, to put forward surveillance programmes to monitor the prevalence of local resistant strains and to guide treatment on the basis of resistance patterns.
The cost of a recurrently bleeding duodenal ulcer (DU) is very high, both from a human and an economic point-of-view. Helicobacter pylori infection plays an important role in the pathogenesis of DU disease and its complications, such as bleeding. Cure of H. pylori infection is recommended in patients with DU and its complications, although in the latter case, the most efficient management is not yet a defined issue. In particular, acid secretion inhibitors may not contribute to long-term cure. Our aims were to ascertain whether the recurrence of bleeding because of DU could be prevented by H. pylori eradication and whether long-term inhibition of gastric acid output is needed to prevent recurrence. Eighty-four patients (65 men; mean age, 55.1 years), who had bled because of recurrent DU, were followed after the cure of H. pylori infection. None of the patients were on therapy with nonsteroidal antiinflammatory drugs. Successful cure of H. pylori was determined by gastroscopy, histology, and serology performed at 3, 6, 12, 24, and 48 months after the eradication treatment. A 13C urea breath test was performed when the results of serology were unclear and also at recurrence of DU or bleeding. After the antibiotic treatment, 46 patients stopped all medications, whereas 38 continued long-term therapy with histamine type 2 receptor antagonists. During a mean follow-up period of 47.2 months (range, 37-65 months), recurrence of DU at endoscopy was observed in three patients in each group (p = 0.56), but none bled again. We conclude that H. pylori eradication prevents DU recurrence and rebleeding, that reinfection rate by H. pylori after cure was nil at 4 years, and that long-term inhibition of acid secretion may not improve outcome after cure of H. pylori, even in patients whose DU was complicated by hemorrhage.
BACKGROUND/AIMS: Laparoscopic cholecystectomy has become the procedure of choice for symptomatic cholelithiasis. A study to evaluate the benefits and risks of laparoscopic cholecystectomy in cirrhotic patients was performed. METHODS: Between January 1994 and December 2000, 1,100 laparoscopic cholecystectomies for symptomatic gallbladder diseases were performed. There were 24 cirrhotic patients (group A) and 72 age- and sex-matched controls (group B). All patients had well-compensated cirrhosis (Child's class A or B). RESULTS: There was no operative mortality in either group and the postoperative complication rates were 20.8 and 9.72% in groups A and B, respectively (p < 0.000001). Operative time in group A was 89.16 vs. 68.41 min in group B (p < 0.000001). The estimated intraoperative blood loss in group A was 106.25 vs. 37.08 ml in group B (p < 0.000001). The average transfusion requirement was 0.155 and 0.0 units in groups A and B, respectively (p < 0.025). The hospital stay in groups A and B was 4.7 and 3.61 days, respectively (p < 0.0500). CONCLUSION: Laparoscopic cholecystectomy in patients with compensated cirrhosis is safe and should be the treatment of choice for these patients. Laparotomy should be applied only if the surgeon considers the operation inadequate to be continued laparoscopically.
BACKGROUND: Digestive diseases (GI) have a major impact on public health in Italy. Hospital stay for digestive pathologies parallels that due to cardiovascular causes. Total mortality for GI causes is also very high. The management of GI pathologies is therefore a major task for the National Health System. To the experienced gastroenterologist it is clear that a large number of hospitalisation is linked to a lack of careful outpatient follow-up of diseases such as cirrhosis, ulcerative colitis and peptic ulcer. METHODS: One year of activity of our Gastro-entero-Hepatology outpatient service is examined. The management of the majority of GI diseases is organized in working teams of physicians and surgeons following cohorts of patients suffering of a specific disease. RESULTS: During the year 2000 not only a statistically significant higher number of patients has been examined (p<0.05), in comparison with 1994, but also the hospitalisation rate was lowered resulting in a very significative cost-containment. CONCLUSIONS: The specialization of outpatient activities into working teams offers advantages in terms of more appropriate medical care and cost reduction, partly due to a less frequent hospitalisation. The obvious counterpart was an increase of request of such form of follow-up from patients, resulting in longer delay to the access.
Gastroesophageal reflux disease (GERD) is highly prevalent in the general population. Heartburn and acid regurgitation are considered the typical presentation of GERD, that however might represent a major pathogenic mechanism in patients with chest pain without coronary artery disease. Chest pain in this instance is often successfully treated with high-dose antisecretory drugs, but the pathogenetic mechanism remains unclear. Further research is needed to clarify the role of GERD on the pathogenesis of chest pain and to ascertain whether a medical or surgical anti-secretory treatment could represent a possible approach. Patients with non-cardiac chest pain of unknown origin should be carefully screened for the occurrence of GERD.
BACKGROUND: Liver cirrhosis is a significant cause of death in Italy and one of the most frequent causes of hospitalization. Acute peptic ulcer and upper gastrointestinal bleeding reportedly occur in over 15% of cirrhotic patients. Since Helicobacter pylori (H. pylori) infection strongly correlates with peptic ulcer, we sought to ascertain the seroprevalence of H. pylori infection in cirrhotic patients. METHODS: In a cross-sectional study, we examined 52 consecutive patients (31 female and 21 male, age range 54-82, mean 68.7 years) suffering from hepatitis C virus (HCV)-related cirrhosis attending the Unit of Gastroenterology of the Valduce Hospital of Como (Italy). RESULTS: The prevalence of antibodies against H. pylori was 86.5% (45/52) in the cirrhotics. Of female patients 28/31 (90.3%) were seropositive as compared to 17 of 21 (80.9%) of male patients. CONCLUSIONS: The very high prevalence of H. pylori infection may explain the frequent occurrence of gastroduodenal ulcer in cirrhotic patients.
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The diagnosis of cholelitiasis, more and more common with the wide diffusion of abdominal ultrasound, is often a surprise for the patient as well as for the physician who is sometimes forced to take a therapeutical decision. In the case of dilatation of the biliary duct, the cholangioRM is assuming an increasingly important role, especially before a therapeutical ERCP. The best therapeutical approach seems to be the surgical ablation in laparoscopy in presence of specific signs and symptoms. Indication to surgical ablation is a symptomatic or complicated cholelithiasis, or the history of obstructive pancreatitis. A preventive cholecystectomy can be useful for precancerous lesions.
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BACKGROUND: Hepatitis C virus infection (HCV) is a major cause of chronic liver disease with the risk of evolution towards hepatic cirrhosis and hepatocellular carcinoma. Numerous studies have documented the possibility of HCV transmission through blood transfusions during surgery or during intravenous drug use. The percentage of the risk of sexual transmission, in the general population not presenting the aforesaid risks is still very controversial. The aim of this study was to evaluate the concomitant levels of seropositivity for anti-HCV, in the partners of patients with chronic HCV liver disease, but no history of previous transfusions or use of intravenous drugs. METHODS: The study included 196 anti-HCV positive spouses with a clinical diagnosis of active chronic hepatitis, aged between 20 and 75 years (mean age 53 years, SD+/-11 years). HCV infection was diagnosed by positivity of serum samples for anti HCV (EIA), confirmed by RIBA II and by circulating HCV-RNA detected by polymerase chain reaction (PCR). All partners underwent anti-HCV assay (EIA), confirmed by RIBA II in the event of positivity. RESULTS: The mean period of cohabitation was 27 years (range 3-37, SD+/-9.8 years). The positivity of anti HCV in both subjects affected 11 couples (5.6%). Of these couples, the viral genotype was also available in 3 cases which proved to be identical in the index patient and the partner, whereas it was not possible to identify the genotype in other couples owing to scarce compliance. CONCLUSIONS: The data obtained from this study confirm the possibility of the sexual transmission of HCV. However, in the context of subjects not belonging to "high risk" groups, this method of transmission does not appear to be important if compared with that of other viruses (HBV and HIV).
Hepatocellular carcinoma (HCC) is a long-term consequence of chronic liver disease, whose aetiology could result from viral, environmental and hereditary causes. Viral infection, by itself, could only partially explain the pathogenesis of cirrhosis and HCC. A new aetiologic agent capable of inducing chronic active hepatitis and hepatocellular tumours was discovered: it is a bacterium belonging to the genus Helicobacter, and named H. hepaticus. Presence of sequences belonging to the 16S rRNA of Helicobacter species (spp.) has been demonstrated in liver of most patients with cirrhosis and HCC. H. pylori and related bacteria, such as H. hepaticus, produce toxins that kill hepatocyte by a granulating effect on liver cell lines. In vivo, such toxins might reach the liver through the portal tract, thereby causing hepatocellular damage. The recognition of Helicobacter spp. as a possible risk factor for cirrhosis and HCC might have a practical impact on the general population: the treatment of this infection is easy and far less expensive than liver transplantation or any long term treatment for the other risk factors of HCC. Any confirmation of the involvement of Helicobacter in liver disease would eventually come from the success of culturing the bacterium from liver tissues. Future research is needed to clarify the importance of Helicobacter spp. in respect to the other pathogens already known as causative agents of chronic inflammation of the liver and its long term sequelae, namely cirrhosis and HCC.
BACKGROUND: Helicobacter pylori (H. pylori) infection is one of the most common infections world-wide. A cohort effect model has been proposed to clarify the differences in the prevalence among the different age-class with a rate of infection higher in old individuals than in younger ones. The source of bacterial acquisition as well as the mode of transmission (oral-oral or fecal-oral) are still unknown and studies have confirmed the role of socio-economic factors and characteristics of childhood living conditions for the acquisition of H. pylori. In this study we analysed the age and gender-specific prevalence of H. pylori infection in a population of apparently healthy subjects, i.e. blood donors attending the blood bank of our hospital. METHODS: From April 1995 to July 1995, 619 consecutive volunteer blood donors (523 males, 96 females, mean age 47+/-5.3 years, range 18-65 years), attending the Molinette Hospital's Blood Bank (Torino), were recruited. H. pylori seroprevalence was assessed by presence of antibodies (IgG) against the bacterium in serum, by means of a commercial enzyme linked immunosorbent assay (ELISA, Helori-test Eurospital). RESULTS: The overall H. pylori seroprevalence in the population was 47%: 265/523 males (51%) were seropositive versus 26/96 females (27%) (p<0.0001, OR 2.77 [confidence interval 95% 1.674.61]). When subdivided into sex and decade of age-groups the difference was significative in three subgroups: among male subjects between 20-29 years, male subjects between 40-49 years and male subjects between 50-59 years. The seroprevalence was also significatively higher in older than younger both in males than females. CONCLUSIONS: This study confirms the cohort effect and for a future survey an equilibrated number of persons belonging to the different groups will be planned.
BACKGROUND: The aim of the study was to evaluate the diagnostic role of Kruis score and intestinal ultrasound in young patients with abdominal pain and bowel dysfunction. METHODS: Prospective, double blind, case-control study in 297 consecutive patients with Crohn's disease and irritable bowel syndrome (from 1993 to 1995). INCLUSION CRITERIA: abdominal pain, bowel dysfunction without clear symptoms or signs of organic disease. The final diagnosis is obtained with usual diagnostic criteria and confirmed by at least 2 years of follow-up. Intestinal ultrasound is considered diagnostic of Crohn's disease if bowel wall thickness is = or > 7 mm; the Kruis score is diagnostic for irritable bowel syndrome if = or > 44. RESULTS: To diagnose Crohn's disease, intestinal ultrasound and Kruis score respectively showed sensitivity of 84 and 97%, specificity of 98 and 50%, positive predictive value of 91 and 33%, negative predictive value of 96 and 98%, efficacy of 95 and 60%. Both exams suggest the same diagnosis in 55% of patients with a correct diagnosis of 97%. CONCLUSIONS: The intestinal ultrasound and the Kruis score can be a good diagnostic association in young patients with abdominal pain and bowel dysfunction but without clear symptoms or signs of organic disease. If their diagnostic conclusions are the same (55%), they have a low probability of diagnostic error (3%). If they show a different diagnostic hypothesis, other markers of disease, for example ASCA, can be used.
BACKGROUND: Helicobacter pylori (H. pylori) infection plays an important role in the pathogenesis of chronic gastritis, peptic ulcer disease, MALT lymphoma and gastric cancer. Recently Helicobacter spp. infection has been correlated with cirrhosis, hepatocellular carcinoma and acute myocardial infarction. Several invasive and non-invasive tests have been proposed for the detection of the bacterium. In clinical practice, the selection of the appropriate test will depend on the disease and on cost-effectiveness. Aim of the study was to validate a rapid, salivary test for detecting the presence of antibodies against H. pylori in a population of patients undergoing to the 13C-urea breath test (13C-UBT). METHODS: Saliva and serum samples were obtained from 91 patients (47 females, mean age 53+/-6.7 years) attending the 13C-UBT service between 15 September and 31 November 1999. Thirty-five of them had had a previous diagnosis of peptic ulcer at endoscopy and 46 out of 91 had a diagnosis of histologically confirmed chronic gastritis. 39 out of 91 were dyspeptic patients with no symptoms suspect for peptic ulcer or cancer. Patients were excluded from the 13C-UBT if they had been treated with inhibitors of acid secretion and antibiotics within 30 days before testing. Breath sample were collected at baseline and 30 minutes after the ingestion of orange juice and a 75 mg dose of 13C-labeled urea. The presence in serum of antibodies (IgG) against the bacterium was assessed by means of a commercial enzyme immunosorbent assay with a reported sensitivity of 94% and specificity of 87%. Saliva was collected using a sterile absorbent pad placed between the mandibular gum and the cheek in the mouth and assayed for H. pylori antibodies by an immunochromatographic rapid method. RESULTS: Thirty-seven of the 91 patients were defined positive by 13C-UBT and serological test. Twenty-nine of these 37 were identified as positive by the salivary test. Fifty-four patients were defined as negative but the salivary test identified 13 of them as positive, thereby sensitivity and specificity were 78.3 and 75.9% respectively. The accuracy was 76.9%. Positive predictive value was 69% and negative predictive value 83.6%. CONCLUSIONS: The salivary test could be considered in the ambulatory setting, as a non-invasive tool for the screening of H. pylori infection, when more accurate methods are not available.
Liver cirrhosis is a significant cause of death in Italy and one of the most frequent causes of hospitalization. The burden of cirrhotic patients on the National Health System is extremely high due to the frequent need for medical care. Acute peptic ulcer and upper gastrointestinal bleeding reportedly occur in over one-third of cirrhotic patients. Since Helicobacter pylori (H. pylori) infection strongly correlates with peptic ulcer, we wished to ascertain the prevalence of H. pylori infection in cirrhotic patients. In a case-control study we looked for this infection in 45 consecutive male patients suffering from hepatitis B virus (HBV)-related cirrhosis and 310 sex and age matched blood donors resident in the same area. Antibodies against H. pylori were present in 40/45 (89%) patients and 183/310 (59%) blood donors (P<0.001). This very high prevalence of H. pylori may explain the frequent occurrence of gastroduodenal ulcer in cirrhotic patients. (See Editorial p. 203)
BACKGROUND/AIMS: Liver cirrhosis is a significant cause of death in Italy and one of the most frequent causes of hospitalization. Acute peptic ulcer and upper gastrointestinal bleeding reportedly occur in over one-third of cirrhotic patients. Since Helicobacter pylori (H. pylori) infection strongly correlates with peptic ulcer, we sought to ascertain the prevalence of H. pylori infection in cirrhotic patients. METHODS: In a case-control study, we examined 254 consecutive patients (127 male and 127 female, age range 30-82 years) suffering from hepatitis C virus (HCV)-related cirrhosis and 463 sex- and age-matched patients admitted to the Department of Emergency Care of our hospital (254 male, 209 female, age range 30-79 years) resident in the same area. RESULTS: Antibodies to H. pylori were present in 226/254 (89%) cirrhotic patients and in 275/463 (59%) controls (p<0.0001). The difference was significant both in males and in females. CONCLUSIONS: The very high prevalence of H. pylori infection may explain the frequent occurrence of gastroduodenal ulcer in cirrhotic patients and may possibly determine the prognosis of those who are also infected with HCV.