Very early prediction of response to HCV treatment with PEG-IFN-alfa-2a and ribavirin in HIV/HCV-coinfected patients.

The objective of this study was to find very early viral kinetic markers to predict nonresponse to hepatitis C virus (HCV) therapy in a group of human immunodeficiency virus (HIV)/HCV-coinfected patients. Twenty-six patients (15 HCV genotype-1 and 11 genotype-3) were treated with a 48-week regimen of peginterferon-alfa-2a (PEG-IFN) (180 µg/week) and weight-based ribavirin (11 mg/kg/day). Samples were collected at baseline; 4, 8, 12, 18, 24, 30, 36 and 42 h; days 2, 3, 4, 7, 8, 15, 22, 29, 43 and 57 then weekly and monthly. Five patients discontinued treatment. Seven patients (27%) achieved a sustained virological response (SVR). Nadir HCV RNA levels were observed 1.6 ± 0.3 days after initiation of therapy, followed by a 0.3- to 12.9-fold viral rebound until the administration of the second dose of PEG-IFN, which were not associated with SVR or HCV genotype. A viral decline <1.19 log for genotype-1 and <0.97 log for genotype-3, 2 days after starting therapy, had a negative predictive value (NPV) of 100% for SVR. The day 2 virological response had a similar positive predictive value for SVR as a rapid virological response at week 4. In addition, a second-phase viral decline slope (i.e., measured from day 2 to 29) <0.3 log/week had a NPV = 100% for SVR. We conclude that first-phase viral decline at day 2 and second-phase viral decline slope (<0.3 log/week) are excellent predictors of nonresponse. Further studies are needed to validate these viral kinetic parameters as early on-treatment prognosticators of nonresponse in patients with HCV and HIV.

Tissue and serum immune response in chronic hepatitis C with mild histological lesions.

The immunopathogenesis of chronic hepatitis C virus (HCV) infection is a matter of great controversy and has been suggested to involve a complex balance between cytokines with pro and anti-inflammatory activity. We investigated the expression of inflammatory cells and cytokines in the liver and serum of 51 chronically HCV infected patients and compared them to data from two sets of normal controls: 51 healthy blood donors and 33 liver biopsies of healthy liver donors. We also assessed the relationship between selected cytokines and cell populations in hepatic compartments and the disease stage. Compared with controls, hepatitis C patients had a greater expression of portal TNF-alpha, TGF-beta and CD4(+) and acinar IFN-gamma, TNF-alpha, IL-1beta and IL-4, as well as a higher serum concentration of IL-2, IL-10 and TGF-beta. Significant positive correlations were found between portal CD4+ and TNF-alpha, portal CD8(+) and TGF-beta, portal CD45(+)RO and TNF-alpha, acinar CD45(+)RO and IFN-gamma and acinar CD57(+) and TGF-beta. In conclusion, we have shown that (i) in this sample of predominantly mild disease, the immune response was associated with a pro-inflammatory response pattern, (ii) CD4(+) T-lymphocytes played a major role in orchestrating the immune response and (iii) these events primarily took place in the portal space.

A posterior-based omega-shaped flap vaginoplasty in girls with congenital adrenal hyperplasia caused by 21-hydroxylase deficiency.

OBJECTIVE: To describe a technical modification for constructing a vagina in girls with congenital adrenal hyperplasia caused by 21-hydroxylase deficiency, using a narrower skin base but rich subcutaneous tissue, aiming to obtain both longer and larger vaginal segments with better cosmesis of the external genitalia. PATIENTS AND METHODS: From August 1997 to February 2001, 28 girls (aged 5 months to 17 years) had a neovagina constructed using a posterior-based omega-shaped flap. Twenty-six patients had a low vagina entering into the urogenital sinus and two had a high vagina that entered the urogenital sinus. In those with a high vagina the flap procedure was combined with the Passerini-Glazel technique. All the patients were scheduled for vaginal "calibrations" during the first year after surgery and, according to the result, would then undergo vaginal dilatation. RESULTS: Six children were re-operated; five had plastic surgery to correct genital folds that had regained a scrotal aspect, whereas one with a high vagina developed a urethral stricture, with urinary dribbling and infection, and had the urethra reconstructed. These six children are currently well. No hormone therapy was given to one child for 1 year who is scheduled for further surgery for a re-virilized clitoris. Two patients were lost to follow-up. Up to the last visit, 19 girls had not developed a vaginal stricture and the cosmesis of their external genitalia was deemed good. CONCLUSION: The posterior-based omega-shaped flap enabled both the construction of wider vaginal segments with a low risk of developing stenosis in those with a low vagina, and increased vaginal dimension when associated with the Passerini-Glazel technique for those with a high vagina. However, despite good cosmesis of the external genitalia, the follow-up is too short to confirm whether this technique will meet all the expectations.

Sigmoid reconfigured vaginal construction in children.

PURPOSE: We present a modified technique of sigmoid neovaginal construction in children that protects the sigmoid pedicle from traction, allows easy adjustment of caliber and reorients the mucosal fold in a longitudinal direction. MATERIALS AND METHODS: From 1997 to 2000, 10 genetically male (46 XY) children 1 to 13 years old underwent construction of a neovagina with sigmoid, incorporating the Yang-Monti concept of intestinal reconfiguration. The diagnosis was androgen insensitivity in 7 patients, congenital adrenal hyperplasia in 2 due to 17 alpha-hydroxylase deficiency and 3 beta-hydroxysteroid dehydrogenase deficiency, respectively, and bladder exstrophy in 1 who required sex reassignment. RESULTS: Eight children had an adequate caliber neovagina after an initial period of systematic dilation. In 1 case a relevant stricture required reoperation using the same technique and the outcome was good. In another child a stricture developed in the middle of the reconfigured sigmoid segment and a regular dilation schedule is still being followed after 23 months of followup. CONCLUSIONS: The new sigmoid reconfiguration technique enables the use of smaller dimension intestinal segments and construction of a long vaginal conduit of adequate caliber. Its optimal adequacy for penetration must be assessed in the future after these patients begin sexual activity.