Evaluation of IL-10 and IL-12B Gene Polymorphisms on the Response to the Standard of Care Therapy in Chronic Hepatitis C Patients: An Egyptian Cohort Study.

Background: Interleukin-10 (IL-10) and IL–12B single nucleotide polymorphisms (SNPs) are confirmed to influence the natural history of hepatitis C virus (HCV) infection, and the response to treatment. This work aimed at evaluating the impact of SNPs in IL-10 gene at positions _1082, _819, and_592 and IL-12B gene on the response to the standard of care (SOC) treatment in Egyptian patients with chronic HCV. Methods: Eighty seven patients with chronic HCV treated by SOC therapy and 20 healthy controls were tested for SNPs in IL-10 at _1082 G/A, _819 C/T and_592 C/A and in IL- 12B (30-UTR 1188-A/C) by polymerase chain reaction (PCR). Patients were divided according to their virologic response into 2 groups; group Ι=patients who achieved sustained virologic response (SVR) and group Π = non responder (NR) patients. Results: SNPs of IL-10 at _1082 G/A and_819 C/T showed that; GA and TT genotypes were significantly related to SVR (P=0.001 and 0.007 respectively). IL-12 genepolymorphisms showed that; CC genotype was significantly related to SVR group (P=0.01) while AA genotype was significantly related to NR (P=0.01). Conclusions: Studying SNPs of IL-10_1082 G/A, IL-10_819 C/T and IL-12B (30-UTR 1188-C/A) proved GA, TT and CC genotypes, respectively, to be good predictors for SVR. Conversely, SNPs of IL-12 C/A proved AA genotype to be good predictor for NR.

Anatomical Non-Responder to Intravitreal Bevacizumab for Neovascular Age-Related Macular Degeneration

PURPOSE: To analyze the characteristics of anatomical non-response to intravitreal bevacizumab (IVB) in patients with neovascular age-related macular degeneration (AMD). METHODS: Neovascular AMD patients who were treated with IVB were studied. A non-responder was defined as a patient whose eyes had no change in choroidal neovascularization (CNV) lesion size or fluorescein leakage and no change in foveal thickness (FT) after at least two administrations of IVB. Demographic findings and efficacy outcomes were compared between responders and non-responders based on patient gender, age, visual acuity (VA), FT, CNV lesion type, CNV lesion size, presence of serous retinal detachment (SRD), presence of pigment epithelial detachment (PED), PED size, and presence of sub-macular hemorrhage (SMH). RESULTS: Five patients (six eyes; 13.6%) were identified as non-responders to treatment with IVB. The mean age of the non-responder group (75.17 +/- 3.66 yers) was greater (p = 0.237) than that of the responder group (71.89 +/- 8.06 years), and the proportion of occult CNV (85.7% versus 55.3%, p = 0.375) was higher in the non-responder group, although there was no significant difference compared with that of the responder group. The PED size of the non-responder group (4.42 +/- 1.56 mm2) was significantly larger than that of the responder group (1.51 +/- 2.33 mm2, p = 0.001). CONCLUSIONS: The authors report a group of patients in AMD with poor treatment response to IVB. The PED size of the non-responder group was confirmed to be significantly larger than that of the responder group.

Seroconvertion to hepatitis B vaccine after weight reduction in obese non-responder

Decreased responses to hepatitis B vaccine have been associated with some host conditions including obesity. Susceptible non-responders to a primary three-dose vaccine series should be revaccinated. Those who maintain a non-responder condition after revaccination with three vaccine doses are unlikely to develop protection using more doses. This is a description of an obese woman who received six doses of hepatitis B vaccine and persisted as a non-responder. She was submitted to a vertical banded gastroplasty Roux-en-Y gastric bypass Capellas's technique. After weight reduction, she received three additional doses of vaccine and seroconverted. Further studies should help clarify the need to evaluate antibody levels and eventually revaccinate the increasing population of individuals who undergo weight reduction.

A diminuição da resposta à vacinação contra hepatite B já foi relacionada a algumas condições clínicas, inclusive à obesidade. Indivíduos que não responderam à série de três doses devem ser revacinados. Caso continuem não-respondedores após duas séries de vacina, não há indicação de doses adicionais. Esta é a descrição de mulher obesa que não havia soroconvertido após ter recebido seis doses de vacina contra hepatite B. Ela foi submetida à gastroplastia em Y de Roux, pela técnica de Capella. Após a redução de peso, a paciente recebeu mais três doses de vacina contra hepatite B e soroconverteu. Novos estudos poderão indicar a necessidade de avaliação de níveis de anticorpos contra antígenos vacinais e eventualmente revacinar esta população cada vez maior de pacientes que se submetem à cirurgia para redução de peso.

Effect of Lamivudine Treatment on Chronic Hepatitis B Infection in Children Unresponsive to Interferon / 대한소아소화기영양학회지

PURPOSE: Interferon is a widely used treatment for chronic hepatitis B in children. However, additional treatment options are needed because more than 50% of hepatitis B patients are unresponsive to interferon. Although lamivudine is widely used to treat hepatitis B, there are few studies on the effect of lamivudine in hepatitis B patients unresponsive to interferon. METHODS: Eight interferon unresponsive patients (6 males and 2 females) were treated with lamivudine (3 mg/kg/day, maximum 100 mg/day) from 6~12 months after interferon treatment was discontinued among 33 children with chronic hepatitis B. They were treated with interferon (interferon alpha-2b, 10 MU/m2 or pegylated interferon 1.5 microgram/kg) for 6 months from January 2000 to December 2007 at the Pusan National University Hospital. The medical records were analyzed retrospectively. RESULTS: The age at treatment with interferon and lamivudine was 4.9+/-3.1 and 6.1+/-3.2 years, respectively. The serum ALT level before treatment with interferon was 148.1+/-105.8 IU/L and the log HBV-DNA PCR mean value was 6.95+/-0.70 copies/mL. The serum ALT level after treatment with interferon was 143.1+/-90.4 IU/L and the log HBV-DNA mean PCR value was 6.46+/-2.08. HBeAg negativization occurred in 2 patients. For all patients, normalization of the serum ALT levels and HBeAg seroconversion (except 2 patients with HBeAg negativization) occurred at 7.4+/-2.1 and 7.9+/-2.1 months respectively after lamivudine treatment. The HBV-DNA PCR became negative in 7 patients (87.5%) at 2.4+/-2.8 months. Complete response was achieved in 7 patients and no recurrence was observed in 2 patients for 3 years after the completion of treatment. Five patients are still under treatment for a mean treatment duration of 24.4+/-9.1 months. In one patient, viral breakthrough occurred and the treatment was stopped. CONCLUSION: The number of patients was small, however, lamivudine treatment in patients with chronic hepatitis B who were unresponsive to interferon was highly effective.

INTRAMUSCULAR VERSUS INTRADERMAL HEPATITIS B REVACCINATION IN HEALTHY NON-RESPONDER CHILDREN:A 5-YEAR PROSPECTIVE RANDOMIZED STUDY / 药物分析学报

Objective With the same times of injection to compare low-dose intradermal regimen with routine-dose intramuscular inoculation in revaccination of non-responders to hepatitis B vaccine. Methods 40 healthy non-responder children collected by screening were administrated a three-dose revaccination randomly by intramuscular or intradermal route (10 vs 2 g per dose), and regularly tested for serologic markers up to five years. By the end of follow-up, a booster dose (5 μg) was given to those who had lost anti-HBs of ≥10 mIU/mL (seroprotection) and anamnestic response was estimated thereafter. Results All 17 intramuscular and 22 of 23 intradermal children effected seroprotection after revaccination. Intradermal children lost seroprotection over time significantly rapider compared with intramuscular children (Log Rank test, P= 0.029). In year 5, 50% of intramuscular but only 18.2% of intradermal children still maintained seroprotection (P=0.075). 12-14 days after the booster dose, all the eight intramuscular children developed an anamnestic response with anti-HBs titer increasing greater, but two of the 18 intradermal children failed to mount seroprotective level. Conclusion Three-routine-dose intramuscular revaccination was significantly effective than low-dose intradermal one with the same times of injection, especially in long-term immunity. We recommend routine-dose intramuscular protocol in revaccination of non-responders.

The Bone Response to Hormone Replacement Therapy according to Basal Bone Mineral Density in Postmenopausal Women / 대한산부인과학회잡지

OBJECTIVE: To investigate the incidence of non-responder to hormone replacement therapy (HRT) and to evaluate the bone response to HRT according to basal bone mineral density(BMD) in postmenopausal women. METHODS: A total of 211 postmenopausal women received either continuous combined estrogen-progestogen replacement (n=112) or estrogen replacement (n=99) for 1 years. BMD at the lumbar spine and femoral neck was measured by dual energy X-ray absorptiometry (DEXA) before and 1 year after HRT. RESULTS: The incidence of non-responder (women with > 3% bone loss per year) to HRT was 9.2% in the lumbar spine, and 23.8% in femoral neck. Estrogen replacement group had a higher incidence of non-responder than combined replacement group. Non-responder group had a higher basal BMD at the lumbar spine than responder group, and showed bone loss rate of 7.6% per year. After 1 year of HRT, postmenopausal women with osteoporosis showed a higher rate of increase in BMD at the lumbar sine and femoral neck than women with normal BMD or osteopenia. CONCLUSION: The non-responders to HRT have a higher basal lumbar BMD, compared with responders. The higher basal BMD at the lumbar spine is, the less bone conservation effect of HRT is.

Relationship between Therapeutic Response and Plasma HVA/5-HIAA Ratio in Newly Admitted Schizophrenia / 대한정신약물학회지

Twenty newly admitted acute schizophrenic patients were treated with haloperidol for 6 weeks. HVA and 5-HIAA were sampled at baseline, 3days after initial neuroleptic dose, and after 1, 2, 3, 4, 6 weeks of treatment. Nine patients were classified as responders in this prospective haloperidol treatment trial. They had a score of change in the BPRS total scores of 25% or greater. Eleven patients were classified as nonresponders, based on a score of changes in the BPRS total scores of less than 25%. 1) There was no significant difference in plasma HVA/5-HIAA ratio between responder and non-responder before and after haloperidol treatment. 2) There was no significant correlations between plasma HVA/5-HIAA ratio and BPRS total scores. This study could not support the hypothesis that neuroleptic treatment would be effective by changing dopamine and serotonin function and/or by altering their interaction.