This Month in Gastroenterology

Abstract

The use of low-dose aspirin in the prevention of cardiovascular disease is frequently associated with the development of dyspeptic symptoms and erosions or ulcerations in the upper gastrointestinal tract. Eradication of Helicobacter pylori and long-term maintenance therapy with proton pump inhibitors (PPI) are effective in the prevention of aspirin-induced gastrointestinal lesions and symptoms in patients with a history of aspirin-induced erosions or peptic ulcer. The potential role of H2-receptor antagonists after healing of aspirin induced peptic ulcer or erosions is unclear. In this issue of Gastroenterology, Ng et al report the results of a randomized, double-blind, controlled study comparing the efficacy of high-dose famotidine with pantoprazole in the prevention of recurrent dyspeptic or complicated ulcer/erosions in patients taking low-dose aspirin. Consecutive patients at a single center in Hong Kong with a history of aspirin (80–320 mg/d) related peptic ulcers/erosions, with or without a history of bleeding, were randomized to receive 80 mg of aspirin with either 40 mg of famotidine or 20 mg of pantoprazole daily for 48 weeks. The end points were the presence of ulcer complications and the severity of ulcer complications. Patients with peptic ulcerations received a healing dose of PPI for 8 weeks. Those who were H pylori positive received an initial 7 days standard PPI-based triple therapy followed by 7 weeks of PPI therapy alone. A total of 161 patients were randomized in a 4-year period. Sixty-five patients in each arm completed the study. The 2 treatment groups were comparable in terms of baseline demographics, clinical presentation, and comorbidities. The prevalence of significant dyspepsia or peptic ulceration was significantly higher in the famotidine group compared with the pantoprazole group (20% vs 0%; 95% confidence interval, 0.1184–1.0; P < .0001; Figure 1). These findings demonstrate that high dose famotidine therapy is inferior to PPI therapy (pantoprazole) in preventing recurrence of aspirin-related peptic ulcer/erosions. PPIs rather than H2 receptor antagonists are recommended in the prevention of recurrent low-dose, aspirin-induced upper gastrointestinal injury. Seepage 82. Ribavirin plus peginterferon, of which 2 commercially available forms are available, is the treatment of choice for chronic hepatitis C virus (HCV) infection. Controlled trials have shown that combination therapy of ribavirin with both peginterferon α2a and peginterferon α2b is safe and effective in the treatment of HCV. It is unclear whether different outcomes are associated with the use of peginterferon α2a or peginterferon α2b. In this issue of Gastroenterology, 2 controlled trials, which compared the efficacy and safety of peginterferon α2a or peginterferon α2b in combination with identical doses of ribavirin in patients with chronic HCV infection, are presented. In study 1, a single-center trial from Italy, 302 consecutive interferon-naïve patients with chronic HCV were randomised to receive ribavirin (1000 mg/d, or 1200 mg/d if >75 kg body weight) plus peginterferon α2a 180 μg once weekly or peginterferon α2b 1.5 μg/kg once weekly for 24 weeks in genotypes 2 or 3 and 48 weeks in genotypes 1 or 4. End of treatment response and sustained virological response were defined, respectively, as a negative qualitative HCV-RNA at the end of treatment and after 24 weeks of untreated follow-up. An end of treatment response was obtained in 83.8% of patients treated with peginterferon α2a compared to 64.4% of patients treated with peginterferon α2b (difference 19.4%; 95% confidence interval [CI],: 9.8%–28.5%; P < .0001). HCV genotypes 1, 2, 3, and 4 were found in 56%, 31%, 11%, and 2% of patients, respectively. A sustained virologic response was obtained in respectively 68.8% and 54.4% (difference between both groups 14.4%; 95% CI, 3.7%–24.6%; P = .008; Figure 2). Male gender, absence of cirrhosis, treatment with peginterferon α-2A, and infection with genotypes 2 or 3 were all independently associated with sustained virologic response. Tolerance and adverse events were comparable between both groups. In study 2, another single-center trial from Italy, 447 previously untreated patients with chronic HCV were randomized to receive ribavirin (1000 mg/d, or 1200 mg/d if >75 kg body weight) plus peginterferon α2a 180 μg once weekly or ribavirin (600 mg/d if <65 kg body weight, 800 mg if 65–85 kg, or 1000 mg/day if >75 kg body weight) plus peginterferon α2b 1.5 μg/kg once weekly for 48 weeks in genotypes 1 or 4. Patients with genotypes 2 or 3 received a 24-week treatment; doses according to body weight were similar. Response definitions were similar to those used in study 1. Patients treated with peginterferon α2a showed higher rates of sustained virological response than patients treated with peginterferon α2b (66% vs 54%; P = .02; odds ratio, 1.71; 95% CI, 1.14–2.57; Figure 1). Age <40 years, pretreatment HCV-RNA <600,000 IU/mL, genotypes 2 and 3, and treatment with peginterferon α2a were all independently associated with sustained virologic response. Tolerance and adverse events were comparable between both groups. Both single-center studies from Italy confirm efficacy of the combination of ribavirin with peg-interferon α2a or α2b, with a similar safety profile of the 2 preparations. In the patients selected for these studies, the rate of sustained virological response is higher with peg-interferon α2a compared with peg-interferon α2b. The difference was mainly apparent in patients infected with genotype 1 and 2, while similar rates of sustained virologic response were obtained in patients infected with genotype 3 and 4. Seepages 108and116. Pathogenic bacteria can enter through the gastrointestinal tract, particularly the small intestine after ingestion to cause watery or bloody diarrheal and other intestinal diseases. Bacteria are thought to be processed by M cells, specialized epithelial cells located in Peyer's patches that overlie follicles to allow exposure to dendritic cells, macrophages, and T and B lymphocytes to trigger an appropriate immune response. In regards to dendritic cells, the population of cells around the follicle have not been previously characterized. In the study by Lelouard et al, noninfected and Salmonella typhimurium-infected intestinal samples were analyzed by immunohistochemistry, confocal microscopy, and flow cytometry. By analyzing lysozyme expression, a subset of cells that expressed lysozyme M (as compared with lysozyme P that is located in Paneth cells) was identified in the overlying subepithelial dome and germinal centers of follicles. Additionally, using widely used myeloid markers (CD11c, CD11b, F4/80, and CX3CR1) 4 distinct subsets of myeloid cells and 5 distinct subsets of myeloid cells were found in the villi and interfollicular regions. In germinal centers, markers identified tingible body macrophages that contain high amounts of lysozyme that phagocytize apoptotic B cells. A unique previously uncharacterized population of CD11c+ CX3CR1+ in the subepithelial dome overlying follicles that expressed lysozyme was identified. These cells also uniquely contained high surface levels of MHC-II, CD40, and CD80 markers, showed active phagocytosis of microspheres (Figure 3) and S typhimurium bacteria (highest of any subset of dendritic cells), and contained high amounts of nuclear debris in the upper part of the dome where epithelial cells die, including M cells. These findings were replicated in the mouse, rat, and human. The study indicates that a unique, distinct population of dendritic cells exist in the subepithelial dome overlying germinal centers of follicles that express lysozyme and function in clearance of bacteria and dead epithelial cells. These specialized cells, which also express major histocompatibility complex II antigens, may play a key role in innate immune defense while linking to adaptive immune responses. Seepage 173. Hepatitis C virus (HCV) infection can cause a chronic hepatitis in approximately half of patients infected, but some patients spontaneously clear the viremia without medical intervention. It has been controversial whether protective immunity exists to prevent HCV reinfection, particularly among intravenous drug users, who have the highest exposure and infection rates of HCV in the United States. In the study by Osburn et al, 22 young intravenous drug users were part of a cohort that was prospectively enrolled in an acute HCV study, and were initially anti-HCV antibody and HCV RNA negative. Patients were followed as controls (undetectable antibody or RNA for ≥60 days), chronic infection (continuous or recurrent viremia with same HCV), or reinfection (new viremia with a genetically unique HCV who had spontaneous clearance of the primary infection followed by ≥60 days of no viremia). Excluding the larger chronically infected group, 11 (50%) patients were reinfected with HCV (5 with a different subtype or genotype), and 11 (50%) showed no new viremia. Reinfection was associated with increases of at least 2.5-fold in alanine aminotransferase, but of 12 reinfections analyzed (2 patients had 2 episodes of reinfection), 10 reinfections were controlled spontaneously and only 2 resulted in persistent viremia. HCV RNA levels during reinfection were ∼3 logs lower compared with initial infection, and the duration of viremia on reinfection was markedly shorter than primary infection (Figure 4). Reinfection was associated with a greater number of T-cell responses, irrespective of whether the same or a new virus was involved, and in some subjects the generation of cross-reactive neutralizing antibodies was associated with clearance of reinfection. This study indicates that control of an initial HCV infection in intravenous drug users is associated with a subsequent, abbreviated viremia and a higher rate of HCV clearance than an initial infection. Initial spontaneous viral clearance occurred in 25% of subjects, compared with 83% of subjects with reinfection. This study suggests a role for adaptive immune responses that help to protect subjects from HCV reinfection. Seepage 315. Famotidine Is Inferior to Pantoprazole in Preventing Recurrence of Aspirin-Related Peptic Ulcers or ErosionsGastroenterologyVol. 138Issue 1PreviewLittle is known about the efficacy of H2-receptor antagonists in preventing recurrence of aspirin-related peptic ulcers. We compared the efficacy of high-dose famotidine with that of pantoprazole in preventing recurrent symptomatic ulcers/erosions. Full-Text PDF Randomized Study of Peginterferon-α2a Plus Ribavirin vs Peginterferon-α2b Plus Ribavirin in Chronic Hepatitis CGastroenterologyVol. 138Issue 1PreviewRibavirin (RBV) combined with either pegylated interferon (PegIFN) α2a or PegIFNα2b is the standard of care for chronic hepatitis C virus (HCV) infection. Due to the lack of head-to-head studies, the 2 PegIFNs have not been directly compared. The endpoints of our study were safety and antiviral efficacy of the 2 regimens. Full-Text PDF Peginterferon Alfa-2a Plus Ribavirin Is More Effective Than Peginterferon Alfa-2b Plus Ribavirin for Treating Chronic Hepatitis C Virus InfectionGastroenterologyVol. 138Issue 1PreviewPatients with chronic hepatitis C virus (HCV) infection are frequently treated with a combination of pegylated interferon (peginterferon) and ribavirin. This study compared the efficacy and safety of peginterferon alfa-2a and peginterferon alfa-2b, each in combination with ribavirin. Full-Text PDF Pathogenic Bacteria and Dead Cells Are Internalized by a Unique Subset of Peyer's Patch Dendritic Cells That Express LysozymeGastroenterologyVol. 138Issue 1PreviewLysozyme has an important role in preventing bacterial infection. In the gastrointestinal tract, lysozyme is thought to be mainly expressed by Paneth cells of the crypt epithelium. We investigated its expression in the Peyer's patch, a major intestinal site of antigen sampling and pathogen entry. Full-Text PDF Spontaneous Control of Primary Hepatitis C Virus Infection and Immunity Against Persistent ReinfectionGastroenterologyVol. 138Issue 1PreviewWe followed patients with ongoing hepatitis C virus (HCV) exposure following control of an initial HCV infection to determine whether primary control conferred protection against future persistent infections. Full-Text PDF