No beneficial effects of amantadine in treatment of chronic hepatitis C patients.

BACKGROUND: Benefit of adding amantadine to antiviral therapy for hepatitis C is controversial. AIMS: We aimed to examine whether such policy enhances sustained viral response in treatment-naïve patients. METHODS: 297 naïve hepatitis C patients were randomized for treatment with amantadine 200mg or placebo, combined with weight-based ribavirin and 12-day high-dose interferon alpha-2b induction therapy, followed by PEG-interferon alpha-2b (1.5 microg/kg/week up to 26 weeks and thereafter, 1.0 microg/kg/week until week 52). Treatment was discontinued if hepatitis C virus (HCV) RNA was positive at week 24. RESULTS: 49% of patients were (former) drug users. Genotype 1 occurred in 45%, high viral load in 70% and severe fibrosis/cirrhosis in 32%, without differences between amantadine or placebo groups. 90 patients prematurely discontinued treatment, mainly because of grade 3 or 4 toxicity. Intention-to-treat analysis revealed sustained viral response in 47% and 51% of amantadine and placebo groups (p=0.49). Amantadine did not enhance sustained viral response in patients with genotype 1 or high viral load nor did it improve primary non-response, breakthrough or relapse rates. Genotype non-1 and lower pre-treatment gamma GT levels were independent predictors for sustained viral response. CONCLUSION: Adding amantadine to antiviral therapy of previously untreated chronic hepatitis C patients has no beneficial effects.

Gamma-glutamyltransferase and rapid virological response as predictors of successful treatment with experimental or standard peginterferon-alpha-2b in chronic hepatitis C non-responders.

BACKGROUND: High-dose peginterferon-alpha (PegIFN-alpha) induction and prolongation of therapy may be an option to improve sustained virological response (SVR) rates among hepatitis C virus (HCV) non-responders, although a higher and a longer dosing of PegIFN-alpha may intensify side effects. METHODS: We randomized 53 patients, who previously failed with standard IFN-alpha+/-ribavirin, to a high-dose induction and an extended regimen with PegIFN-alpha-2b [3.0 microg/kg once weekly (q.w.) 12 weeks-->2.0 microg/kg q.w. 12 weeks-->1.5 microg/kg q.w. 48 weeks] or a standard regimen (1.5 microg/kg q.w. 48 weeks). All patients received daily weight-based ribavirin (800-1200 mg/day). The short-form 36 health survey was used to evaluate health-related quality of life (HRQL). RESULTS: Intention-to-treat analysis showed no significant difference in SVR rate (44% vs. 37%, P=0.62) and relapse rate (9% vs. 31%, P=0.17) between experimental and standard treatment. Overall, 80% of the [positive predictive value (PPV)] patients with rapid virological response (RVR, HCV-RNA negativity at week 4) achieved SVR. No significant dose-related differences in HRQL were seen between both groups. At baseline, genotype 2 or 3 [odds ratio (OR): 7.4, 95% confidence interval (CI): 1.4-33.3, P=0.01] and gamma-glutamyltransferase (GGT) levels <2 x ULN (upper limit of normal) (OR: 6.76, 95% CI: 1.5-31.3, P=0.009) were significantly associated with SVR. Multivariate logistic regression at week 4 showed that only baseline GGT <2 x ULN (OR: 7.3, 95% CI: 1.4-38.5, P=0.01) and RVR (OR: 15.6, 95% CI: 3.2-76.9, P<0.001) were independently predictive for SVR. CONCLUSION: Retreatment with PegIFN-alpha-2b and ribavirin for a minimum of 48 weeks should be considered in all patients unresponsive to previous IFN-based therapies. Baseline GGT values and RVR are highly predictive for retreatment outcome.

MR colonography with limited bowel preparation: patient acceptance compared with that of full-preparation colonoscopy.

PURPOSE: To prospectively evaluate participants' experience and preference of magnetic resonance (MR) colonography with limited bowel preparation compared with full-preparation colonoscopy in participants at increased risk for colorectal cancer. MATERIALS AND METHODS: This study had institutional review board approval; all participants gave written informed consent. In this multicenter study, consecutive participants undergoing conventional colonoscopy because of a personal or family history of colorectal cancer or adenomatous polyps underwent MR colonography 2 weeks prior to colonoscopy. They all followed a low-fiber diet and were given lactulose and an oral contrast agent (fecal tagging with gadolinium) 2 days before colonography. Before imaging, spasmolytics were administered intravenously, and a water-gadolinium chelate mixture was administered rectally for distention of the colon. Breath-hold T1- and T2-weighted sequences were performed in the prone and supine positions. Participant experience in terms of, for example, pain and burden was determined by using a five-point scale and was evaluated with a Wilcoxon signed rank test; participant preference was determined by using a seven-point scale and was evaluated with the chi2 statistic after dichotomizing. RESULTS: Two hundred nine participants (77 women, 132 men; mean age, 58 years; range, 23-84 years) were included. One hundred forty-eight participants received sedatives (midazolam) and/or analgesics (fentanyl) during colonoscopy. Participants rated the MR colonography bowel preparation as less burdensome (P<.001) compared with the colonoscopy bowel preparation (10% and 71% of participants rated the respective examinations moderately to extremely burdensome). Participants also experienced less pain at MR colonography (P<.001) and found MR colonography less burdensome (P<.001). Immediately after both examinations, 69% of participants preferred MR colonography, 22% preferred colonoscopy, and 9% were indifferent (P<.001, 69% vs 22%). After 5 weeks, 65% preferred MR colonography and 26% preferred colonoscopy (P<.001). CONCLUSION: Participants preferred MR colonography without extensive cleansing to colonoscopy immediately after both examinations and 5 weeks later. Experience of the bowel preparation and of the procedure was rated better.