[Discussion on optimal duration of pegylated interferon α combined with ribavirin for chronic hepatitis C in HIV-infected patients].

Objective: To investigate the optimal duration of pegylated-alpha interferon (Peg-INFα) combined with ribavirin (RBV) in treating chronic hepatitis C infection in human immunodeficiency virus (HIV)-infected patients. Methods: A multicenter prospective study was conducted. The study subjects were divided into two groups; HIV/HCV co-infections (Group A, n = 158) and control with HCV-monoinfections (Group B, n = 60). All recruited patients received standard Peg-INFα plus RBV therapy. Group A was divided into 3 subgroups according to CD4(+) cell counts: A1 subgroup, 79 cases, CD4(+) counts > 350 cells /µl, who received anti-HCV before combination antiretroviral therapy(cART); A2 subgroup, 45 cases, CD4(+) counts between 200 and 350 cells/µl, who did not start anti-HCV until they could tolerate cART well; A3 subgroup, 34 cases, CD4(+) counts < 200 cells /µl, cART was administered first, and anti-HCV therapy was started when CD4(+) counts > 200 cells/µl. The anti-HCV efficacy of two groups and 3 subgroups were compared. Statistical analysis for normal distribution and homogeneity of variance data was calculated by t-test and the counting data was analyzed by χ (2) test. The Mann-Whitney U test was used for non-normal data. A one-way analysis of variance (ANOVA) was used for the comparison of multiple groups, followed by SNK method. Multiple independent samples were used for non-parametric tests. Results: There was no significant difference in age and baseline HCV RNA levels between groups and subgroups (P > 0.05). By an intent-to-treat (ITT) analysis, in Group A, the ratio of complete early virological response (cEVR) rate was 75.3% (119/158), the ratio of end of treatment virological response (eTVR) rate was 68.4% (108/158), and the ratio of sustained virological response (SVR) rate was 48.7% (77/158); in Group B, the ratio of cEVR rate was 93.3% (56/60), the ratio of eTVR rate was 90.0% (54/60), and the ratio of SVR rate was 71.7% (43/60); The therapeutic index of Group A were lower than those of Group B (P≤0.05). By per-protocol (PP) analysis, the ratio of cEVR rate in Group A [75.2% (88/112)] was still lower than that in Group B [93.3% (56/60)], but no significant differences were found in the ratio of eTVR rate and SVR rate between 2 groups (P > 0.05). Comparing the efficacy of subgroups (A1, A2 and A3) by ITT analysis, the ratios of cEVR rate were respectively 78.5% (62/79), 75.6% (34/45) and 67.6% (23/34); the ratios of eTVR rate were respectively 68.4%(54/79), 80.0%(36/45)and 52.9%(18/34); and the ratios of SVR rate were respectively 41.8%(33/79), 64.4%(29/45)and 44.1%(15/34). The ratio of eTVR in subgroup A2 was obviously higher than that in subgroup A3 and the ratio of SVR in subgroup A2 was statistically higher than that of subgroup A1(P≤0.05). However, by PP analysis, no significant differences of the therapeutic indexes were found among the respective subgroups (P > 0.05). Conclusion: HIV-HCV co-infected patients would have better anti-HCV efficacy with Peg-INFα-2a plus RBV than HCV- monoinfected patients. The best time for initiating anti-HCV therapy in HIV-HCV co-infected patients is when CD4(+) counts 200 cells/ µl.

[Clinical efficacy of pegylated interferon in patients co-infected with HIV and HCV who failed standard interferon therapy].

OBJECTIVE: To investigate the efficacy and safety of pegylated interferon-alpha (PEG-INF-α) combined with ribavirin in patients co-infected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) who failed prior standard interferon therapy. METHODS: A prospective study was performed to analyze HCV RNA load, liver function, and CD4+ count at weeks 0 (baseline), 12, 24, and 48 of treatment and at 24 weeks after drug discontinuation in 20 patients co-infected with HIV and HCV who failed standard interferon therapy and were then treated with PEG-INF-αand ribavirin. RESULTS: Among the 20 patients, 14 were infected with HCV genotype 1b, 3 with HCV genotype 2a, and 3 failed sequencing. At baseline, the mean CD4(+)count, mean CD8(+)count, and mean CD4(+)/CD8(+)ratio were 406.45 ± 210.83 cells/ml, 1 076.45 ± 716.18 cells /ml, and 0.43 ± 0.17, respectively; the mean HCV RNA load was 6.01 ± 1.13 log10IU/ml; 12 patients (60%) had abnormal liver function. A total of 14 patients (70%) achieved complete early virologic response, 15 (75%) achieved end-of-treatment virologic response, 7 (35%) achieved sustained virologic response (SVR), and 8 (40%) experienced recurrence. The incidence rate of drug-related adverse events during the treatment was 50% (10/20); no serious adverse events occurred, and no patient withdrew from the treatment due to adverse events. At week 48, both CD4(+)and CD8(+)counts of all patients declined significantly compared with the baseline values (P= 0.001 and 0.001), but the CD4(+)/CD8(+)ratio increased significantly (P= 0.032). The SVR group had a significantly lower mean baseline HCV RNA load than the non-SVR group (4.95 ± 1.18 log10IU/ml vs 6.59 ± 0.53 log10IU/ml,t= 3.49,P= 0.009). CONCLUSION: In the patients co-infected with HIV and HCV who failed standard interferon therapy, PEG-INF-αcombined with ribavirin has good efficacy and safety, and the patients with a low baseline HCV RNA load are more likely to achieve SVR.

Three-dimensional geometry of the Heineke-Mikulicz strictureplasty.

BACKGROUND: The objective of this study was to assess the regional geometry of the Heineke-Mikulicz (HM) strictureplasty. The HM intestinal strictureplasty is commonly performed for the treatment of stricturing Crohn's disease of the small intestine. This procedure shifts relatively normal proximal and distal tissue to the point of narrowing and thus increases the luminal diameter. The overall effect on the regional geometry of the HM strictureplasty, however, has not been previously described in detail. METHODS: HM strictureplasties were created in latex tubing and cast with an epoxy resin. The resultant casts of the lumens were then imaged using computed tomography. Using 3-dimensional vascular reconstruction software, the cross-sectional areas were determined and the surface geometry was examined. RESULTS: The HM strictureplasty, while increasing the lumen at the point of the stricture, also results in a counterproductive luminal narrowing proximal and distal to the strictureplasty. Within the model used, cross-sectional area was diminished 25% to 50% below baseline. This effect is enhanced when 2 strictureplasties are placed in close proximity to each other. CONCLUSIONS: The HM strictureplasty results in alterations in the regional geometry that may result in a compromise of the lumen proximal and distal to the location of the strictureplasty. When 2 HM strictureplasties are created in close proximity to each other, care should be undertaken to assure that the lumen of the intervening segment is adequate.

Property changes of UHMW polyethylene hip cup endoprostheses during implantation.

In this study it is demonstrated that the combined chemical and mechanical influences of the implant situation cause property changes of ultra-high-molecular-weight polyethylene (UHMW PE) hip joint cups. Nearly 30 out of 48 loosened cups, retrieved 3 weeks to 11 years after implantation, were investigated. Density measurements show a density increase with implantation time and a dependence of these changes from implant position and loading conditions. The rate of extractable constituents also increases with course of time. An increased in vivo conditioned oxidation of the UHMW PE can be demonstrated by infrared (IR) spectrometry. The density increase can be explained by post-crystallization, which is the result of oxidative chain scission. This leads to a reduction of the average molecular weight of the PE and to an increased extractability of constituents. Since these changes have been recognized as the reasons for aging and failing of UHMW PE, the methods of material characterization used in this study for retrieved implants will help to develop suitable in vitro testing and simulating methods. They are the prerequisite for the necessary improvements of the material properties of UHMW PE.