19 G nitinol needle versus 22 G needle for transduodenal endoscopic ultrasound-guided sampling of pancreatic solid masses: a randomized study.

BACKGROUND: The aim of this prospective multicenter study was to compare a flexible 19 G needle with nitinol shaft (19 G Flex) with a standard 22 G needle for transduodenal endoscopic ultrasound (EUS)-guided sampling of pancreatic head tumors. METHODS: Patients with pancreatic head tumors requiring tissue diagnosis were randomized into two arms: puncture with either a 19 G Flex needle or a 22 G needle. The primary end point was diagnostic accuracy for malignancy. The secondary end points were ergonomic scores, sample cytohistological quality, and complications. A 6-month follow-up was performed. RESULTS: 125 patients were randomized and 122 were analyzed: 59 patients in the 19 G Flex arm and 63 patients in the 22 G arm. The final diagnosis was malignancy in 111 patients and benign condition in 11. In intention-to-treat analysis, the diagnostic accuracy for malignancy of the 19 G Flex and 22 G needles was 69.5 % (95 % confidence interval [CI] 56.1 % - 80.8 %) vs. 87.3 % (95 %CI 76.5 % - 94.4 %), respectively (P = 0.02). In per-protocol analysis excluding eight technical failures in the 19 G Flex group, the diagnostic accuracy of the 19 G Flex and 22 G needles was not statistically different: 80.4 % (95 %CI 66.9 % - 90.2 %) vs. 87.3 % (95 %CI 76.5 % - 94.4 %; P = 0.12). Technical success was higher in the 22 G arm than in the 19 G Flex arm: 100 % (95 %CI 94.3 % - 100 %) vs. 86.4 % (95 %CI 75.0 % - 94.0 %), respectively (P = 0.003). Transduodenal EUS-guided sampling was more difficult with the 19 G Flex (odds ratio 0.68, 95 %CI 0.47 - 0.97). CONCLUSION : The 19 G Flex needle was inferior to a standard 22 G needle in diagnosing pancreatic head cancer and more difficult to use in the transduodenal approach.

Neutralizing antibodies to interferon-α and circulating interferon in patients with chronic hepatitis C non-responding to pegylated interferon plus ribavirin re-treated by pegylated interferon-α-2a and ribavirin (ANRS HC16 GAMMATRI substudy).

A lack of antiviral response in patients with chronic hepatitis C treated with pegylated (PEG)-interferon (IFN)-α-2a + ribavirin (RIBA) may be explained by neutralizing antibodies to IFN-α-2a. The aim of this study was to assess neutralizing antibodies to IFN-α-2a and IFN levels in non-responder patients who were re-treated by PEG IFN-α-2a and RIBA for 12 weeks. Non-responders to a first-line treatment of PEG IFN-α-2a + RIBA were included for treatment with PEG IFN-α-2a (180 µg/week) + RIBA (1,000 mg/day if <75 kg, 1,200 mg otherwise) for 48 weeks. HCV RNA was measured at week 12. IFN levels and neutralizing antibodies to IFN-α-2a were measured retrospectively on stored sera at baseline and weeks 4 and 12, using a quantitative sandwich ELISA for neutralizing antibodies to IFN-α-2a. Twenty-three patients were non-responders and 19 patients were responders at week 12 of the initial phase of the second-line treatment. Non-responders and responders did not differ statistically: baseline age (median age 47 vs. 50 years), HCV RNA (median 6.8 vs. 6.4 log(10) copies/ml), gender (70% vs. 73% males), genotype (genotype 1: 91% vs. 80%). The median IFN-α-2a levels (pg/ml) at weeks 0, 4, and 12 (interquartile range) did not differ between the 19 responders to initial phase of second-line treatment and the 23 non-responders: <3.3 (<3.3-371.4), 1457.3 (106.8-3284.8), and 1,652 (90.8-5,000); 84.5 (3.3-277.4), 1407.4 (120.2-2443.4), and 1620.1 (120.2-2287.1), respectively. Among non-selected consecutive non-responder patients, re-treatment with PEG IFN-α-2a + RIBA is associated with virological response regardless of the presence of antibody-mediated resistance to conventional IFN treatment.

Insulin resistance impairs sustained virological response rate to pegylated interferon plus ribavirin in HIV-hepatitis C virus-coinfected patients: HOMAVIC-ANRS HC02 Study.

BACKGROUND: The aim of this study was to assess the effect of insulin resistance (IR) on the response to hepatitis C virus (HCV) therapy in HIV-HCV-coinfected patients. METHODS: A total of 238 HIV-HCV-coinfected patients (74% male, mean +/-sd age 40 +/-5 years, mean alcohol intake <50 g/day and 38% HCV genotype 2 or 3), treated by standard or pegylated interferon-alpha2b plus ribavirin during 48 weeks were studied. Liver biopsies were assessed before treatment. Patients were considered to have IR when the homeostasis model assessment of IR (HOMA-IR) was >2.5. Multiple logistic regression with stepwise selection was used to estimate independent factors associated with sustained virological response (SVR). RESULTS: IR was present in 32% and significant liver fibrosis (Metavir>or=F2) in 74% of patients. Patients with SVR (96/238 [40%]) were more likely to be infected with HCV genotype 2 or 3 (54% versus 27%; P<0.0001), and had more severe liver fibrosis (>or=F3; 45% versus 30%; P=0.03). By multivariate analysis, a HOMA-IR>2.5 had a negative effect on the SVR (odds ratio 0.49 [95% confidence interval 0.26-0.92]; P=0.05). CONCLUSIONS: A high HOMA-IR level is frequently found in HIV-HCV-coinfected patients and is associated with a reduced SVR rate. Improving insulin sensitivity might be a useful adjunct to HCV therapy in HIV-HCV-coinfected patients.

Effect of antiviral treatment on serum markers of liver fibrosis in HIV-hepatitis C virus-coinfected patients: the Fibrovic 2 Study - ANRS HC02.

BACKGROUND: Non-invasive liver fibrosis scores have been proposed as alternatives to liver biopsy (LB) in hepatitis C virus (HCV)-infected patients. Here, we aimed to assess the effect of antiviral treatment on non-invasive serological markers of liver fibrosis in HIV-HCV-coinfected patients. METHODS: We included 114 HIV-HCV-coinfected patients with LBs performed before and 6 months after the end of treatment (week 72; W72). Fibrotest, the Forn's index, age-platelet ratio index, SHASTA, FIB-4, Hepa-score and Fibrometer scores were assessed. There were 29 (25%) patients who achieved sustained virological response (SVR). RESULTS: At baseline (BL), all non-invasive fibrosis scores except the Forn's index did not show significantly lower values in SVR patients. At W72, all non-invasive scores, except Hepascore, showed a significant decrease in SVR patients (P<0.01). There was a significant difference in fibrosis stages on LBs between BL and W72 in SVR and non-SVR patients. CONCLUSIONS: In HIV-HCV-coinfected patients, HCV clearance is associated with a significant reduction in non-invasive fibrosis serological markers, which most likely reflect the histological improvement associated with SVR. If confirmed, such results will reinforce the reliability of these markers in the follow-up after HCV treatment.

Add-on peg-interferon leads to loss of HBsAg in patients with HBeAg-negative chronic hepatitis and HBV DNA fully suppressed by long-term nucleotide analogs.

BACKGROUND AND OBJECTIVE: The aim of this study was to prospectively evaluate whether the addition of peg-IFN to a stable NA regimen leads to loss of HBsAg in HBeAg-negative patients with chronic hepatitis and HBV DNA fully suppressed by long-term NA treatment. STUDY DESIGN: We analyzed HBsAg levels in 10 HBsAg-positive, HBeAg-negative patients who received peg-IFN alpha-2a in addition to a NA regimen. Treatment lasted a maximum of 96 weeks, according to changes in the HBsAg titer. Before peg-IFN therapy, HBV DNA levels had been below the limit of detection for at least three years. RESULTS: HBsAg levels declined in nine patients. Among these nine, four became HBsAg-negative after 48 weeks of peg-IFN treatment; these patients received peg-IFN for only 48 weeks. NAs were stopped in these four patients, and these levels remained stable for at least 18 months (loss of HBsAg; HBV-DNA negative). HBs seroconversion was observed in two patients. The remaining five patients received 96 weeks of peg-IFN therapy. One patient became HBsAg-negative at the end of peg-IFN therapy; another became HBsAg-negative six months later. Three patients did not become HBsAg-negative. NAs were stopped in the two patients who became HBsAg-negative with no relapse during 12 months of follow up. CONCLUSIONS: In HBsAg-positive, HBeAg-negative patients with HBV DNA were fully suppressed by long-term NA treatment, the addition of peg-INF for a maximum of 96 weeks based on HBsAg-titer monitoring led to a loss of HBsAg and cessation of NA therapy in six out of ten patients, with no relapse for 12-18 months of follow up. HBs seroconversion was observed in two patients.

Assessment of early virological response to antiviral therapy by comparing four assays for HCV RNA quantitation using the international unit standard: implications for clinical management of patients with chronic hepatitis C virus infection.

WHO International Standards for nucleic acid tests are used widely to compare the different assays used in HCV RNA quantitation. The aim of the study was to assess the impact of the international unit standard for measuring HCV RNA in the management of patients with chronic hepatitis C virus (HCV) infection. Twenty-seven naïve patients infected chronically by HCV were treated with ribavirin plus PEG-interferon-alfa-2b for 48 weeks. SVR was obtained for 16 patients (the other were non-responders). For HCV RNA quantitation, four assays were undertaken: Versant HCV RNA 3.0 (Bayer), Real time PCR (TaqMan, Roche), LCx HCV RNA (Abbott), and Cobas Amplicor-Monitor v2 (Roche). Considering a 2-log decline at Week 12 after the beginning of therapy, discordant results were found with the four HCV RNA methods in predicting SVR or non-response. At Week 4 and Week 12, significant differences were observed between Versant HCV RNA 3.0 versus PCR HCV Taqman, Versant HCV RNA 3.0 versus LCx HCV RNA, Cobas Monitor Amplicor HCV 2.0 versus LCx HCV RNA, and Cobas Monitor Amplicor HCV 2.0 versus PCR HCV Taqman (P < 0.001). The HCV RNA cutoff, given a 100% negative predictive value at Week 4 and Week 12, differed with the assays used to quantify HCV RNA, despite the use of the IU/ml units. Eighty-nine percent of serum values for HCV RNA were concordant by the IU standard. All assays, however, failed to detect HCV RNA in some cases. Despite the use of the IU standard HCV-infected patients might be monitored with only one assay.