Safety and efficacy of direct-acting antivirals for the treatment of chronic hepatitis C in a real-world population aged 65 years and older.

The availability of direct-acting antiviral agents (DAA) regimens has expanded the pool of patients eligible for treatment. However, data on the virologic response and tolerability of DAAs in elderly patients are lacking. We evaluated the efficacy and safety of DAAs in patients with advanced fibrosis/cirrhosis in real-life practice with the focus on those aged ≥65 years. Between January and December 2015, all consecutive patients with HCV-related advanced fibrosis/cirrhosis treated with DAA at eleven tertiary referral centres in Emilia Romagna (Italy) were enrolled. Regimen choice was based on viral genotype and stage of disease, according to guidelines. The primary end point was sustained virologic response 12 weeks after the end of treatment (SVR12). Overall, 282 of 556 (50.7%) patients evaluated were elderly, most of them with cirrhosis. Antiviral therapy was stopped prematurely in four (1.4%) patients. Two patients, both with cirrhosis, died during treatment due to worsening of liver/renal function. SVR12 was achieved by 94.7% and was comparable to that obtained in patients aged <65 (P=.074). Similar data were also reported in subgroup of patients aged ≥75 years. All patients with advanced fibrosis achieved virologic response. SVR12 was 80.8% in Child-Pugh-Turcotte (CTP)-B cirrhosis and 95.4% in CTP-A (P=.013). According to genotype, the SVR12 was achieved in 172 of 181 (95%) with genotype 1b cirrhosis and in 44 of 48 (91.7%) with genotype 2 cirrhosis. In conclusions, in a real-world setting, DAAs are safe and effective in elderly patients with HCV-related advanced fibrosis/cirrhosis, but SVR12 is lower with worsening CTP class.

SCCA-IC serum levels are predictive of clinical response in HCV chronic hepatitis to antiviral therapy: a multicentric prospective study.

The combination of pegylated interferon (Peg-IFN) and ribavirin is currently the gold standard therapy in patients with HCV chronic infection. The duration of therapy, as well as the therapeutic dosage, depend on the genotype. Identification of the genotype and rapid virological response (RVR) are widely accepted as the most important predictors of clinical outcome during antiviral therapy but to optimize cost-benefits and to reduce possible side effects, further prognostic factors are needed. Squamous cell carcinoma antigens immunocomplex (SCCA-IC) has been reported to be increased in the serum of patients with liver cancer. In this multicentric prospective study, we investigated the serum levels of SCCA-IC in 103 patients with HCV chronic infection. Serum HCV-RNA was detected before the beginning of treatment, after 4, 12, 24 or 48 weeks, and at week 24 during follow-up. RVR, early virological response and sustained virological response (SVR) were assessed following the international guidelines. SCCA-IC levels were higher in responders (238 AU, interquartile difference 130-556 AU) and decreased significantly to 125 AU (70-290 AU). The mean baseline value in nonresponders was 149 AU (86.5-306.5 AU), but after 4 weeks of treatment the serum levels decreased to 115 AU (80-280 AU): the profile of reduction was different between patients with or without a positive SVR. Logistic regression with SVR as dependent variable identified as significant independent variables: the reduction in SCCA-IC after 1 month (OR = 4.82; 95% CI 1.39-16.67; P = 0.131) and a genotype other than 1 (OR = 0.094; 95% CI 0.21-0.42; P = 0.002); sex and age were also significant factors influencing SVR. SCCA-IC seems to be a reliable independent prognostic marker of therapeutic effectiveness in anti-HCV positive patients undergoing antiviral therapy.

Peginterferon-Α_2B plus ribavirin is more effective than peginterferon-Α_2A plus ribavirin in menopausal women with chronic hepatitis C.

Under-enrolment of women to randomized clinical trials, including chronic hepatitis C, has long been recognized. The aim of this study was to identify factors predictive of sustained virological response (SVR) to PEG IFN/Ribavirin antiviral therapy in relation to gender and reproductive status of female patients involved. Seven hundred and forty-six treatment-naïve patients (431 men, 315 women) treated with Peg-IFNα-2a (180 µg/week) or Peg-IFNα-2b (1.5 µg/kg/week) plus ribavirin (800-1400 mg/day) for 24 or 48 weeks were studied between 2006 and 2010. Differences in SVR rate, overall and by gender were assessed after adjustment and propensity score matching. SVR was obtained in 44.2% of Peg-IFNα-2a-treated patients and in 51.2% of Peg-IFNα-2b-treated patients (intention-to-treat; P = 0.139). Age, fibrosis stage and genotype 2 and 3 were independently associated with SVR by multivariate analysis. Analysing by gender, the difference in SVR between PEG-IFNα types was not significant in men but highly significant in women (Peg-IFNα-2a:39.1%vs Peg-IFNα-2b:54.4%, P = 0.007). This was attributable to a higher SVR rate with Peg-IFNα-2b in the difficult postmenopausal population (26.9% Peg-IFNα-2a vs 46.0% Peg-IFNα-2b, P = 0.040). In women, absence of menopause, genotype 2 hepatitis C virus infection and use of Peg-IFNα-2b were independently associated with SVR. In conclusion, predictive factors for SVR are different in men and women. Factors differing between genders are menopause, severe steatosis and peg-interferon used. The higher SVR rate with Peg-IFNα-2b in menopausal women is likely attributable to more favourable pharmacokinetics that allows Peg-IFNα-2b to reach visceral fat and oppose the increased cytokine production and enhanced inflammatory status in menopause.

Accuracy of breath tests using low doses of 13C-urea to diagnose Helicobacter pylori infection: a randomised controlled trial.

BACKGROUND: The 13C-urea breath test (UBT) for detecting Helicobacter pylori infection is a non-invasive method based on the organism's urease activity. Since its first description, the method has been extensively modified. However, only the dose of 13C-urea and the measurement equipment are directly related to the cost of the test. AIMS: (1) To assess the diagnostic accuracy before eradication therapy of three UBTs using 25, 15, and 10 mg of 13C-urea, respectively; and (2) to determine diagnostic performance in the post-eradication setting showing the highest values for sensitivity and specificity with the lowest dose of 13C-urea. METHODS: Three hundred consecutive patients were randomised to be tested with one of the three UBTs. All patients underwent upper endoscopy with biopsies. A total of 222 more patients were enrolled to evaluate the second aim. Infected patients were offered treatment and asked to return 4-6 weeks after the end of therapy to perform endoscopic follow up and to carry out 13C-UBT. RESULTS: In the pretreatment setting, 13C-UBT 25 mg had a sensitivity of 100% (95% confidence interval (CI) 91.8-100) and a specificity of 100% (95% CI 93.7-100); 13C-UBT 15 mg had a sensitivity of 96.1% (95% CI 86.8-98.9) and a specificity of 100% (95% CI 92.6-100); and 13C-UBT 10 mg had a sensitivity of 89.1% (95% CI 77-95.3) and a specificity of 100% (95% CI 93.3-100). As the test with the best performance and the lowest dose of 13C-urea was 13C-UBT 15 mg, it was evaluated after treatment, reporting a sensitivity of 100% (95% CI 79.6-100) and a specificity of 98.9% (95% CI 94.3-99.8). DISCUSSION: UBTs using 25 and 15 mg of 13C-urea were both accurate in the diagnosis of H pylori infection in untreated patients. 13C-UBT 15 mg was also accurate for follow up of patients after treatment.

Diagnostic accuracy of a new rapid urease test (Pronto Dry), before and after treatment of Helicobacter pylori infection.

AIM: The diagnosis of Helicobacter pylori infection can be made easily by the rapid urease test during endoscopy. The mainly commercial rapid urease test available in routine practice, is in liquid phase, need to be stored at 4 degrees C and generally they are not ready to use. Recently a new rapid urease test, the Pronto Dry, has been reported to be faster in the final reading, ready to use, and it can be stored at room temperature. Aim of the study was to evaluate the diagnostic accuracy and the reaction time of Pronto Dry vs liquid phase-rapid urease test, before and after treatment of Helicobacter pylori infections. METHODS: A total of 315 untreated dyspeptic patients and 323 post-treatment patients, were enrolled in this study. At endoscopy, 5 biopsy samples were obtained from the antrum and from the corpus for histology; culture and rapid urease tests (liquid phase and Dry test). Helicobacter pylori status was defined according to European guidelines. Sensitivity and specificity of both rapid urease test were assessed at 5, 15, 30 minutes, and 3 and 24 hours after the endoscopy. RESULTS: One hundred and eleven out of 315 untreated dyspeptic patients were found to be positive for Helicobacter pylori infection, and 56/323 patients were found still positive after treatment. Sensitivity at 5, 15, 30 minutes, and 3 and 24 hours in untreated patients were 45%, 71.2%, 81.1%, 90.1% and 91.9% respectively for the Pronto Dry vs 6.3%, 31.5%, 51.3%, 78.4% and 90.1% for liquid phase rapid urease test. Sensitivity at the same times in not eradicated patients were 33.9%, 66.1%, 85.7%, 92.8 and 92.8% respectively for the Pronto Dry vs 3.6%, 37.5%, 55.3%73.2%, 92.8% for liquid phase rapid urease test. CONCLUSIONS: Pronto Dry showed to have higher sensitivity in pre and post treatment setting compared to liquid phase-rapid urease test within 3 hours of incubation time.

High rate of Helicobacter pylori eradication with sequential therapy in elderly patients with peptic ulcer: a prospective controlled study.

BACKGROUND: Helicobacter pylori eradication rates with triple therapies are decreasing, and few data in elderly patients are available. A 10-day sequential regimen succeeded in curing such H. pylori infection in unselected patients. AIM: To compare this sequential regimen and the standard triple therapy for H. pylori eradication in geriatric patients with peptic ulcer. METHODS: Overall, 179 H. pylori-infected patients with peptic ulcer were enrolled (mean age: 69.5 years; range: 65-83). Patients were randomized to 10-day sequential therapy (rabeprazole 20 mg b.d. plus amoxicillin 1 g b.d. for the first 5 days, followed by rabeprazole 20 mg, clarithromycin 500 mg and tinidazole 500 mg, all b.d., for the remaining 5 days) or standard 7-day triple regimen (rabeprazole 20 mg, clarithromycin 500 mg and amoxicillin 1 g, all b.d.). Helicobacter pylori status was assessed by histology and rapid urease test at baseline and 4-6 weeks after completion of treatment. RESULTS: The sequential regimen achieved eradication rates significantly higher in comparison with the standard regimen at both intention-to-treat (94% vs. 80%; P = 0.008) and per-protocol (97% vs. 83%; P = 0.006) analyses. In both treatment groups, compliance to the therapy was high (> 95%), and the rate of mild side-effects was similarly low (< 12%). At repeated upper endoscopy, peptic ulcer lesions were healed in 97% patients, without a statistically significant difference between the sequential regimen and the standard triple therapy. CONCLUSIONS: In elderly patients with peptic ulcer disease, the 10-day sequential treatment regimen achieved significantly higher eradication rates in comparison with standard triple therapy.

A 10-day levofloxacin-based triple therapy in patients who have failed two eradication courses.

BACKGROUND: A standard third-line treatment is lacking, and European guidelines recommend performing culture in these patients. However, the use of this procedure as 'routine practice' is definitively not feasible. AIM: To evaluate the eradication rate of a 10-day levofloxacin-based triple therapy in patients who have failed two eradication courses for Helicobacter pylori. METHODS: A total of 151 patients with persistent Helicobacter pylori infection after two treatments were studied. Patients were considered positive if two of three endoscopic tests were positive. Susceptibility testing was also performed. Patients received a standard dose of proton-pump inhibitors twice daily, levofloxacin 250 mg twice daily and amoxicillin 1 g twice daily, for 10 days. Endoscopic follow-up was carried out 4-6 weeks after the end of eradication therapy. RESULTS: About 76% (95% CI: 68.8-82.3), and 85% (95% CI: 77.5-89.7) of patients were eradicated according to intention-to-treat and per-protocol analysis, respectively. Eradication rates of the strains showed as 92% (95% CI: 83.2-96.7) of those resistant to both metronidazole and clarithromycin but susceptible to levofloxacin. CONCLUSIONS: In patients who failed previous regimens, the 10-day levofloxacin-based triple therapy is safe and effective, allowing eradication in almost 80% of the patients.

Helicobacter pylori infection: anything new should we know?

Over the past year, 2003-4, there have been a number of studies consolidating previous work in relation to pathogenesis of disease, diagnosis and management of Helicobacter pylori. Studies into the pathogenesis of disease have identified the main adhesin of H. pylori as an important virulence marker and as a potential target for therapy. Molecular investigations of both the strain and host variations have identified the action of several of the virulence factors, e.g. cagA, vacA, on disrupting host cell signalling and the consequences in respect of the release of chemokines from the damaged gastric epithelium and the effect on apoptosis. Over the past year, there have been further diagnostic kits developed based on modifications of current technology. Two promising areas of research for diagnosis are the use of host/strain genome polymorphisms as a means of identifying high-risk patients who may develop severe disease and the use of proteomics to identify potential antigens of diagnostic (or therapeutic) use. The three main antibiotics that are used in first-line eradication regimens are clarithromycin, metronidazole and amoxycillin. Of these, metronidazole has the highest prevalence of resistance, followed by clarithromycin; amoxycillin resistance is only rarely reported. The decreasing success of current first-line therapy is the driving force for the development of new antibiotic combinations and a search for novel sources for chemotherapeutic agents and novel therapeutic targets.

A rapid immunochromatographic assay for Helicobacter pylori in stool before and after treatment.

BACKGROUND: Current guidelines recommend non-invasive testing and treatment of young dyspeptic patients without alarm symptoms. AIM: To evaluate the accuracy of a new rapid immunochromatographic stool test to diagnose Helicobacter pylori infection before and after treatment compared with a gold standard. METHODS: Prospective, single-blind study, performed in a tertiary care hospital. A total of 303 consecutive dyspeptic patients underwent endoscopy with multiple biopsies. Infected patients were offered a treatment and invited to come back 4-6 weeks after the end of therapy to repeat the endoscopy. Patients were also asked to provide a stool sample before and after therapy. RESULTS: About 149 patients were H. pylori infected. The sensitivity and specificity before treatment were 91.3 and 93.5%; after treatment 92 and 100%. The likelihood ratios were robust enough to produce significant changes from pretest to post-test probability both in pre-treatment (LR+ = 14, LR- = 0.093) and post-treatment (LR+ = 19.6, LR- = 0.095). CONCLUSIONS: The novel immunochromatographic stool test is fast, easy to perform and provides good differentiation between positive and negative results. It might become a rapid near patients test easily performed in the doctor office.