Comparative efficacy of long-term antibiotic treatments in the primary prophylaxis of spontaneous bacterial peritonitis.

BACKGROUND & AIMS: Several antibiotic treatments aiming to prevent spontaneous bacterial peritonitis (SBP) in cirrhotic patients with low-protein content in ascitic fluid have been tested; however, there are limited data on the comparative efficacy of these regimens. We assessed their comparative efficacy through a network meta-analysis and using GRADE criteria to appraise quality of evidence. METHODS: Through literature review through October 2018, we identified 10 randomized controlled trials comparing antibiotic treatments (norfloxacin, ciprofloxacin, trimethoprim/sulfamethoxazole and rifaximin) with each other or placebo. Primary outcome was SBP occurrence, with mortality rate and rate of other infections as secondary outcomes. RESULTS: In comparison with placebo, moderate quality evidence supports the use of norfloxacin and ciprofloxacin in primary prophylaxis of SBP (risk ratio 0.23; 95% CI, 0.09-0.56; P = 0.001 and 0.23; 0.07-0.79; P = 0.02 respectively) while only low quality evidence suggests superiority of rifaximin (risk ratio 0.15; 0.05-0.42). When antimicrobial agents were compared to each other, no significant difference was found. With regard to mortality, moderate quality supports the superiority of norfloxacin over placebo (risk ratio, 0.68; 95% CI, 0.47-0.99; P = 0.04), while ciprofloxacin and rifaximin showed only a non-significant benefit and no significant difference was found in the other comparisons. None of the tested antibiotics proved to significantly decrease the rate of other infections. CONCLUSIONS: Norfloxacin appears to have significant benefit both in terms of SBP prevention and mortality; ciprofloxacin represents a valuable option although without a clear survival benefit. Rifaximin shows interesting results but needs to be tested in further trials.

Individualized treatment with combination of Peg-interferon alpha 2b and ribavirin in patients infected with HCV genotype 3.

BACKGROUND & AIMS: The benefit of individualizing treatment for patients with genotype 3 HCV infection on the basis of viral clearance at week 4 (wk4-R) has not been firmly established. METHODS: Four hundred and fourteen patients received Peg-interferon alpha-2b plus 1000-1200 mg of ribavirin daily according with body weight > or <75 kg. Patients were randomized to standard 24 weeks (Std24) or to a 12 or 36 weeks variable treatment duration (Var12/36). In the variable treatment arm, patients with or without wk4-R were allocated to either 12 or 36 weeks duration. RESULTS: At treatment week 4, HCV RNA was undetectable in 262 patients (63.3%), 136 in the Std24, and 126 in the Var12/36 group (p=0.41). In patients with wk4-R, end-of-treatment (EOT) responses were 80.4% (CI 85.4-95.3) and 97.6% (CI 94.9-99.9) in the two arms, respectively (p=0.019). In patients without wk4-R, corresponding rates were 61.9% (50.6-73.2) and 75.3% (CI 65.9-84.6) (p=0.08). SVR was attained in 302 patients, 71.4% (CI 65.3-77.6) in the St24 group and 74.3% (CI 58.4-80.3) in the variable 12/36 arm. Among patients with wk4-R, SVR was 81.6% (CI 75.1-88.1) and 82.5% (75.9-89.1), respectively. In patients without wk4-R, SVR amounted to 52.1% (CI 40.4-63.7) and 61.7 (CI 51.1-72.3) in the two arms (p=0.25). CONCLUSIONS: HCV genotype 3 patients with week4-R may be treated safely with 12 weeks of therapy, provided that sufficiently high doses of ribavirin are administered. For patients still viremic at treatment week 4, SVR rates were numerically higher after 36 weeks of treatment than after the currently recommended 24 weeks.

Comparison between Y90 Radioembolization Plus Sorafenib and Y90 Radioembolization alone in the Treatment of Hepatocellular Carcinoma: A Propensity Score Analysis.

BACKGROUND: Adjuvant sorafenib may enhance the efficacy of transarterial radioembolization with yttrium-90 in hepatocellular carcinoma patients. The aim of this study is to assess the efficacy and safety of radioembolization plus sorafenib in comparison to radioembolization alone. METHODS: Out of 175 hepatocellular carcinoma (HCC) patients treated with radioembolization between 2011 and 2018, after propensity score matching, two groups were compared: a group of 45 patients that underwent radioembolization while being on sorafenib (Group 1) and a second group of 90 patients that underwent radioembolization alone (Group 2). RESULTS: Baseline characteristics of the two groups were well balanced concerning liver function and tumor burden. No significant differences in survival outcomes were identified (median overall survival 10 vs. 10 months; p = 0.711), median progression-free survival 6 vs. 7 months (p = 0.992) in Group 1 and Group 2). The objective response rate in Group 1 vs. Group 2 was 45.5% vs. 42.8% (p = 1) according to mRECIST. No differences in toxicity nor in liver decompensation rates were registered. CONCLUSIONS: The association of sorafenib does not prolong survival nor delay progression in patients treated with radioembolization. Liver toxicity does not differ among the two therapeutic schemes.

Correction: SVR12 rates higher than 99% after sofosbuvir/velpatasvir combination in HCV infected patients with F0-F1 fibrosis stage: A real world experience.

[This corrects the article DOI: 10.1371/journal.pone.0215783.].

SVR12 rates higher than 99% after sofosbuvir/velpatasvir combination in HCV infected patients with F0-F1 fibrosis stage: A real world experience.

BACKGROUND AND OBJECTIVES: The pangenotypic single tablet regimen of NS5B inhibitor sofobuvir (SOF) and NS5A inhibitor velpatasvir (VEL) is advised for 12 weeks in HCV-infected patients including those with compensated cirrhosis. Addition of ribavirin (RBV) may be considered in genotype 3 (GT3) with compensated and is recommended in decompensated cirrhosis. Real-life results with SOF/VEL are limited. To evaluate efficacy and safety in a large real-world-cohort including patients with different GTs and various fibrosis stages. DESIGN: In total, 1429 patients were treated with SOF/VEL 400/100 mg for 12 weeks in the Puglia registry between June 2017 and May 2018. 1319 (92.3%) reached week 12 post-treatment (SVR12) at the moment. Only 41 received RBV. Diagnosis of cirrhosis was based on transient elastography and/or APRI or FIB-4 scores. Sensitivity analysis in the population including all patients except non virological failure was conducted. Primary efficacy endpoint was the percentage of patients with SVR12. RESULTS: Patients' mean age was 63.8 years, 42.3% had GT1. The majority were naïve and 735 (55.5%) F0/F2. Of the remaining 587, 282 had cirrhosis. SVR12 was 98.5%, 98.0% in GT1, 99.4% in GT2, 97.1% in GT3, 100% in GT4. Overall, SVR12 by sensitivity analysis was 99.4%; 99.7% among F0-F1. Among 218 PWID, SVR12 was 94.5%. Discontinuation rates were 3.7% among PWID and 0.7% among non-PWID (p = 0.004). CONCLUSIONS: SOF/VEL treatment of chronic HCV infection reaches very high cure rates in a variety of patients; including those with F0/F1 and PWID.

High doses of interferon in combination with ribavirin are more effective than the standard regimen in patients with HCV genotype 1 chronic hepatitis.

BACKGROUND/AIMS: The aim of the present, open-labelled, controlled study was to determine whether 5 MU of interferon (IFN) alpha 2b combined with a standard dose of ribavirin might increase the rate of viral clearance in all patients with chronic HCV hepatitis or at least in those with an unfavourable genotype. METHODS: A total of 298 previously untreated patients with chronic hepatitis C were randomized to 5 or 3 MU of interferon alpha 2b 3 times per week with 1000-1200 mg of ribavirin daily (148 and 150 patients, respectively). Patients were treated for 12 months and observed for 6 months posttreatment. RESULTS: In patients infected with HCV genotype 1, the sustained virologic response was 37.8% (95% CI 27.3-48.1) with IFN 5 MU and 19.2% (95% CI 10.1-28.2) with IFN 3 MU (P=0.008). Out of 45 sustained responders with genotype 1, 31 (69%) had received 5 MU and 14 (31.1%) the standard 3 MU dose of IFN in combination with ribavirin (P=0.01). Of the 86 responders infected with genotype non-1, 39 (45.3%) were from the 5 MU IFN group and 47 (54.6%) were from the 3 MU IFN group; these figures were not significant. At the multivariate analysis of baseline features for all patients, the variables with an independent effect for a sustained response were genotype non-1 (odds ratio (OR) 3.98, 95% CI 2.36-6.40), and the histological grading (score 0-2) (OR 2.48, 95% CI 1.12-5.51) and staging (score 0-1) (OR 1.73, 95% CI 1.02-2.95). For patients with genotype 1 only the high regimen of IFN entered the model (OR 2.39, 95% CI 1.13-5.05), whereas for patients with genotype non-1 an age of <40 years (OR 2.64, 95% CI 1.23-5.70) and staging (score 0-1) (OR 2.38, 95% CI 1.07-5.28) were independent predictors of a sustained response. CONCLUSIONS: Our study suggests that when treating naive patients with genotype 1, there is a significant increase in the rate of sustained virologic clearance by increasing the dose of IFN given in combination with ribavirin.