IFN-Alpha receptor-1 upregulation in PBMC from HCV naïve patients carrying cc genotype. possible role of IFN-lambda.

BACKGROUND AND AIMS: IL-28B gene polymorphisms predict better therapeutic response and spontaneous clearance of HCV. Moreover, higher expression of IFN-lambda has been reported in patients with the rs12979860 CC favourable genotype. The study aim was to establish possible relationships between IL-28B rs12979860 genotypes and expression of IFN-alpha receptor-1 (IFNAR-1) in naïve HCV patients, and to explore the possible role of IFN-lambda. METHODS: IFNAR-1 mRNA levels were measured in PBMC from naïve patients with chronic hepatitis C with different IL-28 genotypes. The ability of IFN-lambda to up-regulate the expression of IFNAR-1 was established in PBMC from healthy donors carrying different IL-28B genotypes. RESULTS: Lower IFNAR-1 mRNA levels were observed in PBMC from HCV-infected naïve patients as compared to healthy donors. In healthy donors, IFNAR-1 mRNA levels were independent from IL-28B genotype, while in HCV patients, an increasing gradient was observed in TT vs CT vs CC carriers. In the latter group, a direct correlation between IFNAR-1 and endogenous IL-28B expression was observed. Moreover, IFN-lambda up-regulated IFNAR-1 expression in normal PBMC in a time-and dose-dependent manner, with a more effective response in CC vs TT carriers. CONCLUSION: Endogenous levels of IFN-lambda may be responsible for partial restoration of IFNAR-1 expression in HCV patients with favourable IL-28 genotype. This, in turn, may confer to CC carriers a response advantage to either endogenous or exogenous IFN-alpha, representing the biological basis for the observed association between CC genotype and favourable outcome of either natural infection (clearance vs chronicization) or IFN therapy.

Gastric low-grade mucosal-associated lymphoid tissue-lymphoma: Helicobacter pylori and beyond.

The stomach is the most frequently involved site for extranodal lymphomas, accounting for nearly two-thirds of all gastrointestinal cases. It is widely accepted that gastric B-cell, low-grade mucosal-associated lymphoid tissue (MALT)-lymphoma is caused by Helicobacter pylori (H. pylori) infection. MALT-lymphomas may engender different clinical and endoscopic patterns. Often, diagnosis is confirmed in patients with only vague dyspeptic symptoms and without macroscopic lesions on gastric mucosa. H. pylori eradication leads to lymphoma remission in a large number of patients when treatment occurs at an early stage (I-II(1)). Neoplasia confined to the submucosa, localized in the antral region of the stomach, and without API2-MALT1 translocation, shows a high probability of remission following H. pylori eradication. When both bacterial infection and lymphoma recur, further eradication therapy is generally effective. Radiotherapy, chemotherapy and, in selected cases, surgery are the available therapeutic options with a high success rate for those patients who fail to achieve remission, while data on immunotherapy with monoclonal antibodies (rituximab) are still scarce. The 5-year survival rate is higher than 90%, but careful, long-term follow-up is required in these patients since lymphoma recurrence has been reported in some cases.

Second-line and rescue therapies for Helicobacter pylori eradication in clinical practice.

BACKGROUND AND AIMS: A levofloxacin-based triple therapy and a rifabutin-based regimen are advised as second-line and rescue therapies in the current Italian guidelines for H. pylori eradication. However, no data are available for the efficacy of these treatments in clinical practice. METHODS: A total of 86 consecutive patients who failed a standard, first-line, triple therapy for H. pylori infection were treated with a 10-day triple therapy including omeprazole 20 mg, amoxycillin 1 g, and levofloxacin 250 mg or 500 mg, each given twice daily. Eradication failure patients received a 10-day rescue therapy with omeprazole 20 mg, amoxycillin 1 g, and rifabutin 150 mg, each given twice daily. A further therapeutic attempt was performed with a 14-day, high-dose dual therapy (esomeprazole 40 mg and amoxicillin 1 g, each thrice daily). RESULTS: Following the second-line therapy, H. pylori infection was cured in 76.4% (95% CI = 67.8-85.0) and 79.5% (95% CI = 70.8-88.2) at intention-to-treat (ITT) and per-protocol (PP) analysis, respectively. After the rescue therapy, bacterial eradication was achieved in 84.6% (95% CI = 65-100). Two patients with persistent infection were successfully cured with the high-dose dual therapy. CONCLUSION: The efficacy of levofloxacin-based second-line therapy seems to be decreasing, whilst rescue therapy with rifabutin would appear a valid third-line therapy, and a high-dose dual therapy may be used as a further rescue therapy.

Helicobacter pylori antibiotic resistance and [13C]urea breath test values.

A correlation between delta over baseline (DOB) values of the [(13)C]urea breath test (UBT) and Helicobacter pylori clarithromycin resistance has been reported, suggesting a possible predictive role of UBT in therapeutic outcome. However, available data are limited and conflicting. This study aimed to clarify this issue, assessing the possible relationship between H. pylori resistance towards different antibiotics (clarithromycin, metronidazole and levofloxacin) and UBT values. The data showed similar DOB values between susceptible and resistant strains for clarithromycin (46.9+/-32.3 vs 45.7+/-30.6; P=0.8), metronidazole (46.4+/-29.6 vs 47.4+/-37.9; P=0.8), and levofloxacin (45.0+/-30.2 vs 54.2+/-38.4; P=0.08). Likewise, comparable DOB values were observed between susceptible and multidrug-resistant strains (45.4+/-29.6 vs 54.8+/-44.8; P=0.1). In conclusion, our data failed to find a significant correlation between UBT values and H. pylori antibiotic resistance.

Primary low-grade and high-grade gastric MALT-lymphoma presentation.

GOAL: To assess the clinical and endoscopic presentation of primary gastric lymphoma. BACKGROUND: Remission rate and long-term survival in patients with gastric lymphoma mainly depend on disease stage at diagnosis. Series reporting clinical and endoscopic presentation of gastric lymphoma are generally small and heterogeneous. STUDY: Systematic review with pooled-data analysis assessing clinical and endoscopic presentation of primary gastric lymphoma. RESULTS: Data regarding 2000 patients were collected. Overall, males were slightly more prevalent, alarm symptoms were absent in near half of the patients, lymphoma was diagnosed in a stage >I in one-third of the patients, and Helicobacter pylori infection was present in 88.8% of considered patients. At endoscopy, the ulcerative type was the most frequent presentation, although low-grade lymphoma was diagnosed on normal/hyperemic gastric mucosa in 9% of cases. Patients with high-grade lymphoma presented alarm symptoms (anemia and/or melena and/or hemorrhage, persistent vomiting, weight loss), an exophytic or ulcerative lesion, a stage III-IV, and a H. pylori negative status more frequently than low-grade lymphoma cases. CONCLUSIONS: Our pooled-data analysis showed that gastric lymphoma is still disappointingly diagnosed in an advanced stage in a large number of patients. This is probably due to presence of nonspecific symptoms at initial clinical presentation and/or a normal appearing mucosa at endoscopic observation in the early stages.

Systemic thrombolysis of portal vein thrombosis in cirrhotic patients: a pilot study.

BACKGROUND: Portal vein thrombosis is a frequent complication in liver cirrhosis. Encouraging reports of systemic thrombolysis in non-cirrhotic patients suffering from acute portal vein thrombosis led us to start a pilot study on the efficacy and safety of systemic low dose recombinant tissue plasminogen activator (Actilyse, Boheringer Ingelheim, Florence, Italy). PATIENTS: Nine cirrhotic patients (6 males and 3 females) with recent portal vein thrombosis were enrolled. Exclusion criteria were portal cavernomatosis, recent (30 days) surgery, active bleeding, hepatocellular carcinoma and cancer in other sites. METHODS: All cases were treated for a maximum of 7 days by continuous i.v. infusion of 0.25mg/kg/die of r-tPA plus subcutaneous low molecular weight heparin. Efficacy was evaluated by colour doppler sonography monitoring and confirmed by contrast enhanced computerized tomography. RESULTS: The combined r-tPA/LMWH treatment was well tolerated without clinically significant side effects. Complete resolution of thrombosis occurred in 4 cases, partial regression in 4 and none in 1. Retreatment of a complete recurrence in 1 patient was successful. Variceal pressure dropped from 30.7+/-4.5 mmHg to 21.2+/-6.6 mmHg (p=0.012). CONCLUSIONS: Our preliminary data demonstrate that thrombolytic treatment of recent portal vein thrombosis with i.v. r-tPA and LMWH in patients with cirrhosis appears to be safe and effective and can significantly reduce pressure in oesophageal varices.

Effects of Helicobacter pylori eradication on early stage gastric mucosa-associated lymphoid tissue lymphoma.

BACKGROUND & AIMS: Different remission rates of gastric low-grade, B-cell, mucosa-associated lymphoid tissue (MALT) lymphoma have been reported after Helicobacter pylori eradication. We assessed the long-term remission and relapse rates of early stage MALT lymphoma in patients treated only by H pylori eradication and identified factors that might predict outcome. METHODS: This systematic review analyzed data from 32 studies, including 1408 patients. RESULTS: The MALT lymphoma remission rate was 77.5% (95% confidence interval, 75.3-79.7), and was significantly higher in patients with stage I than stage II(1) lymphoma (78.4% vs 55.6%; P = .0003) and in Asian than in Western groups (84.1% vs 73.8%; P = .0001). Neoplasia confined to the submucosa regressed more frequently than that with deeper invasion (82.2% vs 54.5%; P = .0001); patients with lymphoma localized to the distal stomach experienced regression more frequently than those with lymphoma of the proximal stomach (91.8% vs 75.7%; P = .0037). The remission rate was higher among patients without the API2-MALT1 translocation than in those with this translocation (78% vs 22.2%; P = .0001). In an analysis of data from 994 patients, 7.2% experienced lymphoma relapse during 3253 patient-years of follow-up evaluation, with a yearly recurrence rate of 2.2%. Infection and lymphoma were cured by additional eradication therapy in all patients with H pylori recurrence (16.7%). Five (0.05%) of the patients initially cured of lymphoma developed high-grade lymphoma within 6 to 25 months of therapy. CONCLUSIONS: H pylori eradication is effective in treating approximately 75% of patients with early stage gastric lymphoma. Long-term follow-up evaluation of these patients is needed to detect early lymphoma relapse or progression.

Treatment of low-grade gastric MALT-lymphoma unresponsive to Helicobacter pylori therapy: a pooled-data analysis.

The most favourable therapeutic strategy for gastric MALT-lymphoma not responding to Helicobacter pylori eradication still remains unclear, neither official guidelines nor randomised studies being available. We therefore performed a systematic review of the literature to evaluate the efficacy of different therapeutic approaches in these patients. Data regarding 315 patients were valuable, and lymphoma remission following the first therapeutic attempt was achieved in 90.1% cases. The most used therapy was radiotherapy (112 patients), followed by surgery (80 patients) and chemotherapy (68 patients), whilst a combination therapy was less frequent. Radiotherapy achieved a higher remission rate as compared to chemotherapy (97.3 vs. 85.3%; P = 0.007), being similar to surgery (97.3 vs. 92.5%; P = 0.2). No difference emerged when comparing lymphoma remission rate achieved by a single therapy with that of combined treatments (89.6 vs. 96.4%; P = 0.6). This is the first pooled-data analysis assessing the efficacy of different oncologic therapeutic approaches to treat gastric MALT-lymphoma unresponsive to H. pylori eradication. Radiotherapy seems to be the most suitable treatment in these patients.

Eradication therapy for Helicobacter pylori in patients with gastric MALT lymphoma: a pooled data analysis.

OBJECTIVES: Helicobacter pylori eradication is recognized as the initial therapy for gastric low-grade, B-cell, mucosa-associated lymphoid tissue (MALT) lymphoma. This study assesses (i) the H. pylori eradication rates for various first- and second-line and rescue therapies and (ii) the associated reinfection rates in patients. METHODS: Pooled data analysis of systematic review of the literature was performed in this study. RESULTS: Data from 34 studies with 1,271 treated patients were used. After first-line therapy, the infection was cured in 91% (95% confidence interval (CI)=89.4-92.5) of cases, the eradication rate being higher after dual therapy compared with the 7- or 14-day triple therapies (P=0.0525). After second-line therapy, the eradication rate was 80.8% (95% CI=82.7-95.1), being higher after triple rather than quadruple therapy. Further therapies (from three to five attempts) cured the infection in 75% of patients. H. pylori infection was ultimately cured in 1,250 patients, resulting in eradication rates of 98.3% (95% CI=97.6-99) and 99.8% (95% CI=99.6-100) at intention-to-treat and per-protocol analysis levels, respectively. Bacterial reinfection occurred in 18 (2.7%; 95% CI=1.4-3.9) of 676 patients who were followed-up (0.7% yearly). Overall, gastric lymphoma remission was achieved in 973 (77.8%) of 1,250 patients successfully cured of H. pylori infection. CONCLUSIONS: This was the first comprehensive ( approximately 1,300 patients) analysis of the therapeutic management of H. pylori in gastric lymphoma patients. Data suggest that this infection is easily managed in these patients, being cured in nearly all cases.