Biochemical criteria at 1 year are not robust indicators of response to ursodeoxycholic acid in early primary biliary cirrhosis: results from a 29-year cohort study

Background: In primary biliary cirrhosis (PBC), biochemical criteria at 1 year are considered surrogates of response to ursodeoxycholic acid (UDCA). However, due to the slow natural history of PBC, evaluation at 1 year may be suboptimal to assess the therapeutic response, particularly in early disease. Aim: To determine whether evaluation of biochemical criteria at 1 year is a reliable surrogate of UDCA response in early PBC. Methods: We analysed the prospectively collected data of 215 patients (untreated = 129; UDCA-treated = 86) with early PBC (normal baseline bilirubin/albumin) and a median follow-up of 8 years (range: 1–29.1). The 1-year attainment rates of the Barcelona, Paris-I, Paris-II and Toronto definitions, and their predictive relevance for a poor outcome (death, transplantation, complications of cirrhosis), were assessed either as a result of UDCA or no treatment. Independent associations with attaining each UDCA response definition were identified by multivariate analysis. Results: Untreated patients displayed 1-year biochemical features compatible with ‘treatment response’ at rates (Barcelona: 36.4%, Paris-I: 66.7%, Toronto: 59.7%, Paris-II: 40.3%) similar to those obtained under UDCA. Depending on the definition, baseline ALP≤3xULN (OR: 4.80–35.90), AST≤2xULN (OR: 5.63–9.34) and early histological stage (OR: 3.67–3.87) were the stronger predictors for attaining the criteria. UDCA treatment was associated with attaining Barcelona (OR = 2.16) and Paris-II (OR = 2.84), but not Paris-I, and not Toronto definition when excluding late histological cases. Paris-I criteria were significantly predictive of long-term outcomes (HR = 2.83) in untreated patients. Conclusions:In early PBC, biochemical criteria at 1 year reflect severity of the disease rather than the therapeutic response to UDCA

Impact of Safety-Related Dose Reductions or Discontinuations on Sustained Virologic Response in HCV-Infected Patients: Results from the GUARD-C Cohort.

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced ≥1 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with ≥1 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not ≥5. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin.This study was sponsored by F. Hoffmann-La Roche Ltd, Basel, Switzerland. Support for third-party writing assistance for this manuscript, furnished by Blair Jarvis MSc, ELS, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland

Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

Background: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. Methods: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. Results: SVR24 rates were 46.1 % (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1,2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. Conclusions: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginter-feron alfa-2a/ribavirin

Factors that may affect treatment outcome of triple Helicobacter pylori eradication therapy with omeprazole, amoxicillin, and clarithromycin

Factors affecting Helicobacter pylori eradication rate With omeprazole (OME), clarithromycin (CL), and amoxicillin (AMO) have not been extensively studied. We have investigated the effect of age, sex, smoking, ulcer disease, compliance with therapy, H. pylori colonization density, degree and activity of antral gastritis, the coexistence of corpus gastritis, and the presence of lymphoid follicles on H. pylori eradication rate. We studied 80 consecutive H. pylori-positive patients, with duodenal ulcer (N = 35) or nonulcer dyspepsia (N = 45) treated with OME 20 mg, CL 500 mg, and AMO 1 g, each given twice daily for 10 days. H. pylori was eradicated in 71/80 (88.8%, 95% CI 82-96%) patients. The regimen failed to eradicate the only strain (1.8%, 95% CI 0-5.2%) that was clarithromycin resistant. Multivariate discriminant analysis showed that two histological variables (Wilks lambda = 0.74, chi(2) = 23.41, df = 2, P &lt; 0.001), absence of lymphoid follicles in routine gastric biopsies (F = 13.63, P &lt; 0.001) and coexistence of antral and body gastritis (F = 13.68, P &lt; 0.001), significantly increased H. pylori eradication rate. No other factor examined predicted H. pylori eradication with this regimen. Our data suggest that body gastritis is a positive and presence of lymphoid follicles in routine gastric biopsies is a negative predictive factor of treatment outcome with the omeprazole, clarithromycin, and amoxicillin regime

Effectiveness of two quadruple, tetracycline- or clarithromycin-containing, second-line, Helicobacter pylori eradication therapies

Background: There are no guidelines on second-line therapies for Helicobacter pylori eradication failures of omeprazole-clarithromycin-amoxicillin triple therapy. Aim: To compare the efficacy of two second-line therapies for persistent H. pylori infection. Methods: Over a 6-year period, patients with persistent H. pylori infection following omeprazole-clarithromycin-amoxicillin eradication therapy were randomized to receive omeprazole, 20 mg twice daily, bismuth, 120 mg four times daily, metronidazole, 500 mg twice daily, and either tetracycline, 500 mg four times daily, or clarithromycin, 500 mg twice daily, given for 7 days. Before therapy, patients underwent endoscopy with biopsies for histology, culture and antibiotic susceptibility tests. H. pylori infection was confirmed by histology. Results: Of the 95 randomized patients, 88 (93%,) completed the study. Age, sex, smoking, ulcer/non-ulcer dyspepsia ratio and antibiotic resistance were not significantly different between the treatment groups. On intention-to-treat analysis, eradication was achieved in 41 of the 49 patients (84%: 95% confidence interval, 70.4-92.79%) and 27 of the 46 patients (59%; 95%, confidence interval, 43.3-73.0%) of the tetracycline and clarithromycin-containing groups, respectively (P = 0.007). On multivariate regression analysis, the sensitivity of H. pylori to metronidazole had a likelihood ratio of 5.2 (P = 0.022), followed by the type of quadruple therapy (likelihood ratio, 4.4; P = 0.036). Conclusions: Tetracycline-containing quadruple rescue therapy is highly effective in treating H. pylori eradication failures of the omeprazole-amoxicillin-clarithromycin regimen