Comparison of diode laser - Oral tissue interaction to different wavelengths. In vitro study of porcine periodontal pockets and oral mucosa.

BACKGROUND: The aim of this in vitro study was to evaluate the effect of diode lasers at different wavelengths and power settings in handmade incisions in periodontal pockets and in oral mucosa of porcine tissue considering thermal damage, necrosis and the affected area of the soft tissue. MATERIAL AND METHODS: Combining the following laser wavelengths, 445nm, 532nm (KTP), 810nm, 980nm, 1064nm and 1470nm, and a power range from 0.5W to 2.0W in a continuous wave mode (CW), we made handmade incisions in porcine periodontal pockets and oral mucosa. After histological processing, we measured the area of ​​lost tissue, the area of ​​thermal damage and the area of ​​necrosis. Then, we performed ANOVA to evaluate the difference between groups and two-way ANOVA to identify the influence of the laser-type variables and the power on the results. RESULTS: We applied an ANOVA test to evaluate the results, where statistical analysis showed clear differences between the 1470nm and 810nm laser groups that refer to thermal damage and necrosis in the periodontal pocket surface. Regarding the oral mucosa surface, the 1064nm laser showed differences in the analysis of lost tissue. According to the applied power, all the variables we studied (lost tissue area, area of thermal damage and necrosis) showed higher values when using a power of 2.0W instead of 0.5W. CONCLUSIONS: According to our results, the 810nm diode laser for oral soft-tissue biopsy using power ranges between 0.5W and 2W would be the best choice to avoid thermal damage in peri-incisional margins.

Clinical experience with integrase inhibitors in HIV-2-infected individuals in Spain.

BACKGROUND: HIV-2 is a neglected virus despite estimates of 1-2 million people being infected worldwide. The virus is naturally resistant to some antiretrovirals used to treat HIV-1 and therapeutic options are limited for patients with HIV-2. METHODS: In this retrospective observational study, we analysed all HIV-2-infected individuals treated with integrase strand transfer inhibitors (INSTIs) recorded in the Spanish HIV-2 cohort. Demographics, treatment modalities, laboratory values, quantitative HIV-2 RNA and CD4 counts as well as drug resistance were analysed. RESULTS: From a total of 354 HIV-2-infected patients recruited by the Spanish HIV-2 cohort as of December 2017, INSTIs had been given to 44, in 18 as first-line therapy and in 26 after failing other antiretroviral regimens. After a median follow-up of 13 months of INSTI-based therapy, undetectable viraemia for HIV-2 was achieved in 89% of treatment-naive and in 65.4% of treatment-experienced patients. In parallel, CD4 gains were 82 and 126 cells/mm3, respectively. Treatment failure occurred in 15 patients, 2 being treatment-naive and 13 treatment-experienced. INSTI resistance changes were recognized in 12 patients: N155H (5), Q148H/R (3), Y143C/G (3) and R263K (1). CONCLUSIONS: Combinations based on INSTIs are effective and safe treatment options for HIV-2-infected individuals. However, resistance mutations to INSTIs are selected frequently in failing patients, reducing the already limited treatment options.

Association between diabetes and nonretention of root filled teeth: a systematic review and meta-analysis.

Previous studies have found an association between the outcome of root canal treatment (RCT) and diabetic status. This systematic review and meta-analysis aimed to analyse the potential relationship between diabetes and the occurrence of extracted root filled teeth (RFT). The clinical PICO question was as follows: in adult patients with RFT, does the absence or presence of diabetes influence the prevalence of RFT extraction? The key words used in the systematic search were as follows: (Diabetes OR Diabetes Mellitus OR Hyperglycaemia OR Diabetic) AND (Endodontic OR Endodontics OR Endodontic Treatment OR Root Canal Treatment OR Root Canal Preparation OR Root Canal Therapy OR Root Filled Teeth OR Endodontically Treated Teeth) AND (Extraction OR Retention OR Survival OR Success OR Failure OR Outcome). The primary outcome variable was odds ratio (OR) for the frequency of extracted RFT in diabetics and healthy subjects. The method of DerSimonian-Laird with random effects was used to calculate the overall OR. Three hundred titles were identified, and three studies achieved the inclusion criteria. Data from 54 936 root canal treatments, 50 301 in nondiabetic control subjects and 4635 in diabetic patients, were analysed. The calculated overall odds ratio (OR = 2.44; 95% CI = 1.54-3.88; P = 0.0001) implies that diabetics had a significantly higher prevalence of extracted RFT than healthy nondiabetic subjects. The results of available studies indicate a significant relationship between DM and increased frequency of nonretained root filled teeth. Diabetes mellitus should be considered an important preoperative prognostic factor in root canal treatment.

Bacterial translocation and clinical progression of HCV-related cirrhosis in HIV-infected patients.

The aim of the study was to evaluate whether bacterial translocation (BT) predicts the clinical outcome in HIV/HCV-coinfected patients with compensated cirrhosis. A cohort of 282 HIV/HCV-coinfected patients with cirrhosis and no previous liver decompensation (LD) was recruited. Serum levels of the DNA sequences encoding the well-conserved 16S rRNA subunit (16S rDNA), the lipopolysaccharide (LPS) and soluble CD14 (sCD14) at diagnosis of cirrhosis were measured. Primary endpoint was the emergence of the first LD and/or death of any cause. Secondary endpoints were LD, liver-related death (LRD) and death of any cause. After a median (Q1-Q3) follow-up of 51 (27-72) months, 67 patients (24%; 95% CI: 19-29) developed their first LD or died during follow-up. Baseline levels of 16S rDNA, LPS and sCD14 were not associated with the probability of developing the primary endpoint of the study. The mean (SD) survival time free of LD and/or death according to levels of 16S rDNA (<83, 83-196, 197-355, >355 [copies/µL]) was 78 (5), 72 (5), 81 (4) and 82 (4) months, respectively (P = .5). The corresponding figures for LPS (<0.1, 0.1-0.6, 0.6-1.5, > 1.5 [IU/mL]) were 76 (5), 71 (5), 77 (5) and 81 (4) months, respectively (P = .4). Baseline levels of BT serum markers were not associated with any of the secondary endpoints analysed in the study. Thus, BT does not seem to be a relevant predictor of clinical outcome in HIV/HCV-coinfected patients with compensated cirrhosis.

Effectiveness and clinical implications of the use of topical antibiotics in regenerative endodontic procedures: a review.

Regenerative endodontic procedures (REPs) are biologically based procedures planned to replace damaged tissues, including dentinee and root structures, as well as cells of the pulp-dentine complex. Effective sterilization of the root canal is essential in REPs, and antibiotics have been widely used to disinfect root canals. The aim of this paper was to review the scientific literature on (i) Effectiveness of antibiotics used in REPs against bacteria implicated in endodontic disease; (ii) Scientific evidence supporting the use of topical antibiotics in REPs; (iii) Clinical implications of the use of antibiotics in REPs and the possible side effects; (iv) Effect of antibiotics on dental pulp stem cells; and (v) Ongoing research on the use of antibiotics in REPs. Antibiotics used in REPs are effective against bacteria implicated in endodontic infections. Triple antibiotic pastes with minocycline attain complete disinfection of immature teeth with necrotic pulps, without affecting SCAP. Experimental studies carried out in dogs support the use of antibiotics in REPs. Clinical studies report high success rates of RET using antibiotics as intracanal dressings. However, tooth discolouration is an important side effect of the use of TAP. An antibiotic paste containing only metronidazole and ciprofloxacin could be a good alternative to the use of TAP. The use of antibiotic-containing scaffolds or clindamycin-modified triple antibiotic (metronidazole, ciprofloxacin and clindamycin) polymer could be a biologically safe antimicrobial drug delivery system in REPs.

European mitochondrial haplogroups are not associated with hepatitis C virus (HCV) treatment response in HIV/HCV-coinfected patients.

OBJECTIVES: Mitochondria are multifunctional organelles with a key role in the innate immune response against viral infections. Mitochondrial DNA (mtDNA) haplogroups have been related to AIDS progression and CD4 T-cell recovery in HIV-infected patients, and to a delay in the development of liver fibrosis in HIV/hepatitis C virus (HCV)-coinfected patients. We performed a study to investigate whether mtDNA haplogroups may be associated with HCV treatment response in HIV/HCV-coinfected patients on pegylated interferon (pegIFN) plus ribavirin (RBV). METHODS: We performed a retrospective study in 304 patients who completed a course of HCV therapy. mtDNA polymorphisms were genotyped using Sequenom's MassARRAY platform. The interleukin-28B (IL-28B) polymorphism (rs12980275) was genotyped using the GoldenGate® assay. Sustained virological response (SVR) was defined as an undetectable HCV viral load at week 24 after the end of treatment. The statistical analysis was carried out using on-treatment data. RESULTS: The SVR rates were 52.6% (160 of 304) for all patients, and 37.8% (46 of 201) for patients with HCV genotype 1 or 4 vs. 81.4% (83 of 102) for patients with HCV genotype 2 or 3 (P < 0.001). No significant associations were found between mtDNA haplogroup and SVR when all patients were included in the analysis and when patients were stratified by HCV genotype (i.e. those with genotypes 1/4 and 2/3 analysed separately) or IL-28B rs12980275 genotype. CONCLUSIONS: European mtDNA haplogroups were not related to HCV treatment response in HIV/HCV-coinfected patients on pegIFN-α/RBV therapy.

IL28RA polymorphism (rs10903035) is associated with insulin resistance in HIV/HCV-coinfected patients.

Hepatitis C virus (HCV) infection is associated with insulin resistance (IR), although mechanisms leading to IR in these patients are not completely understood. The aim of this study was to evaluate the association of interleukin 28B (IL28B) and interleukin 28 receptor alpha (IL28RA) polymorphisms with IR among human immunodeficiency virus (HIV)/HCV-coinfected patients. We carried out a cross-sectional study on 203 patients. IL28B (rs8099917) and IL28RA (rs10903035) polymorphisms were genotyped by GoldenGate(®) assay. IR was defined as homeostatic model assessment (HOMA) values ≥3.00. Univariate and multivariate generalized linear models (GLM) were used to compare HOMA values and the percentage of patients with IR according to IL28B and IL28RA genotypes. In total, 32% (n = 65/203) of the patients had IR. IL28B rs8099917 TT was not significantly associated with HOMA values and IR. In contrast, rs10903035 AA was significantly associated with high HOMA values taking into account all patients (P = 0.024), as well as the subgroups of patients with significant fibrosis (P = 0.047) and infected with HCV genotype 3 (P = 0.024). Additionally, rs10903035 AA was significantly associated with IR (HOMA ≥3.00) in all patients (adjusted odds ratio (aOR) = 2.02; P = 0.034), in patients with significant fibrosis (aOR = 2.86; P = 0.039) and HCV genotype 3 patients (aOR = 4.89; P = 0.031). In conclusions, IL28RA polymorphism (rs10903035) seems to be implicated in the glucose homeostasis because AA genotype increases the likelihood of IR, but this association was different depending on hepatic fibrosis and HCV genotype.

IL28RA polymorphism is associated with early hepatitis C virus (HCV) treatment failure in human immunodeficiency virus-/HCV-coinfected patients.

Due to the poor rate of response to hepatitis C virus (HCV) with pegylated interferon and ribavirin treatment in HCV/HIV coinfected patients, key factors for predicting failure would be useful. We performed a retrospective study on 291 patients on HCV treatment, who had early virological response (EVR) data. IL28B and IL28RA polymorphisms were performed using the GoldenGate(®) assay. Unfavourable genotypes at IL28B (rs12980275 AG/GG and rs8099917 GT/GG) and an unfavourable allele at IL28RA (rs10903035 G) were associated with early treatment failure. However, only the rs12980275 AG/GG genotype and rs10903035 G allele remained independently associated with early failure in the overall population (OR = 4.15 (95% CI = 1.64-10.54) and OR = 2.00 (95% CI = 1.19-3.36), respectively) as well as in GT1/4 patients (OR = 5.07 (95% CI = 1.81-14.22) and OR = 2.03 (95% CI = 1.13-3.66), respectively). Next, a decision tree showed early treatment failure increased from 37.1% to 65.5% when the unfavourable rs12980275 AG/GG and rs10903035 AG/GG genotypes and HCV-RNA≥ 500.000 IU/mL were taken into account in GT1/4 patients. In contrast, the failure rate decreased from 37.1% to 11.9% when the favourable rs12980275 AA and rs10903035 AA genotypes were detected. The percentage of patients correctly classified was 78.4%, and AUROC was 0.802 ± 0.028. Regarding GT3 patients, the presence of the GCGCA haplotype (all unfavourable alleles) was associated with early treatment failure, while no association was observed for the IL28B polymorphisms. In conclusion, the IL28RA polymorphism was associated with early treatment failure independently of the IL28B SNPs. The combination of IL28B and IL28RA polymorphisms might be a valuable tool for predicting early treatment failure before starting HCV treatment.

Association of torque teno virus (TTV) and torque teno mini virus (TTMV) with liver disease among patients coinfected with human immunodeficiency virus and hepatitis C virus.

Torque teno virus (TTV) and torque teno mini virus (TTMV) have been potentially related to liver diseases. The aim of the study was to quantify TTV and TTMV in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients to study the relationship between the TTV and TTMV viral loads and the severity of liver disease. We carried out a cross-sectional study in 245 patients coinfected with HIV and HCV (HIV/HCV-group), 114 patients monoinfected with HIV (HIV-group), and 100 healthy blood donors (Control-group). Plasma samples were tested for TTV and TTMV by quantitative real-time polymerase chain reaction (PCR). The prevalences of TTV and TTMV infections in the HIV/HCV-group and the HIV-group were significantly higher than the Control-group (p < 0.05). Furthermore, TTV and TTMV coinfections were found in 92.2 % (226/245) in the HIV/HCV-group, 84.2 % (96/114) in the HIV-group, and 63 % (63/100 %) in the Control-group (p ≤ 0.05). HIV/HCV-coinfected patients with HIV viral load ≥50 copies/mL and patients with severe activity grade had the highest viral loads of TTV and TTMV (p ≤ 0.05). HIV/HCV-coinfected patients with high TTV load (>2.78 log copies/µL) had increased odds of having advanced fibrosis or severe necroinflammatory activity grade in the liver biopsy. Moreover, HIV/HCV-coinfected patients with high TTMV load (>1.88 log copies/µL) had decreased odds of having no/minimal fibrosis and no/mild activity grade, and increased odds of having a high fibrosis progression rate. In conclusion, TTV and TTMV might play a role in the development of liver disease in immunodeficiency patients, such as the patients coinfected with HIV and HCV.

Outcome of HCV/HIV-coinfected liver transplant recipients: a prospective and multicenter cohort study.

Eighty-four HCV/HIV-coinfected and 252-matched HCV-monoinfected liver transplant recipients were included in a prospective multicenter study. Thirty-six (43%) HCV/HIV-coinfected and 75 (30%) HCV-monoinfected patients died, with a survival rate at 5 years of 54% (95% CI, 42-64) and 71% (95% CI, 66 to 77; p = 0.008), respectively. When both groups were considered together, HIV infection was an independent predictor of mortality (HR, 2.202; 95% CI, 1.420-3.413 [p < 0.001]). Multivariate analysis of only the HCV/HIV-coinfected recipients, revealed HCV genotype 1 (HR, 2.98; 95% CI, 1.32-6.76), donor risk index (HR, 9.48; 95% CI, 2.75-32.73) and negative plasma HCV RNA (HR, 0.14; 95% CI, 0.03-0.62) to be associated with mortality. When this analysis was restricted to pretransplant variables, we identified three independent factors (HCV genotype 1, pretransplant MELD score and centers with <1 liver transplantation/year in HIV-infected patients) that allowed us to identify a subset of 60 (71%) patients with a similar 5-year prognosis (69%[95% CI, 54-80]) to that of HCV-monoinfected recipients. In conclusion, 5-year survival in HCV/HIV-coinfected liver recipients was lower than in HCV-monoinfected recipients, although an important subset with a favorable prognosis was identified in the former.

Liver retransplantation in HIV-infected patients: a prospective cohort study.

Information regarding liver retransplantation in HIV-infected patients is scant. Data from 14 HIV-infected patients retransplanted between 2002 and 2011 in Spain (6% retransplantation rate) were analyzed and compared with those from 157 matched HIV-negative retransplanted patients. In HIV-infected patients, early (≤30 days) retransplantation was more frequently indicated (57% vs. 29%; p = 0.057), and retransplantation for HCV recurrence was less frequently indicated (7% vs. 37%; p = 0.036). Survival probability after retransplantation in HIV-positive patients was lower than in HIV-negative patients, 42% versus 64% at 3 years, although not significantly (p = 0.160). Among HIV-infected patients, those with undetectable HCV RNA at retransplantation and those with late (>30 days) retransplantation showed better 3-year survival probability (80% and 67%, respectively), similar to that in their respective HIV-negative counterparts (72% and 70%). In HIV-infected and HIV-negative patients, 3-year survival probability in those with positive HCV RNA at retransplantation was 22% versus 65% (p = 0.008); in those with early retransplantation, 3-year survival probability was 25% versus 56% (p = 0.282). HIV infection was controlled with antiretroviral therapy after retransplantation. In conclusion, HIV-infected patients taken as a whole have unsatisfactory survival after liver retransplantation, although patients with undetectable HCV RNA at retransplantation or undergoing late retransplantation show a more favorable outcome.

Impact of inosine triphosphatase gene variants on the risk of anemia in HIV/hepatitis C virus-coinfected patients treated for chronic hepatitis C.

The role of rs1127354/rs7270101 alleles at the inosine triphosphatase (ITPA) gene on ribavirin-induced anemia was assessed in 74 patients with hepatitis C virus and human immunodeficiency virus coinfection. Anemia developed in 80% of patients with normal ITPA activity compared with 33% of those with reduced ITPA activity. In contrast, ITPA variants did not influence sustained virological response.

Use of transient elastography (FibroScan®) for the noninvasive assessment of portal hypertension in HIV/HCV-coinfected patients.

The hepatic venous pressure gradient (HVPG) is the gold standard for assessing portal pressure and correlates with the occurrence of portal hypertension (PH)-related complications. Transient elastography (TE) is a new, highly accurate noninvasive technique, which enables us to evaluate hepatic fibrosis to detect advanced fibrosis and cirrhosis. We performed a hepatic haemodynamic study and TE in 38 HIV/HCV-coinfected patients. The association between HVPG and liver stiffness was assessed by linear regression. The diagnostic value of TE was assessed by receiver operating characteristic (ROC) curves. We considered clinically significant PH as an HVPG ≥ 10 mmHg and severe PH as an HVPG ≥ 12 mmHg. A total of 38 HIV/HCV-coinfected patients were included. Twenty-eight patients (73.7%) had clinically significant PH (HVPG ≥ 10 mmHg), and 23 (60.5%) of these had severe PH (HVPG ≥ 12 mmHg). We found a statistically significant association between liver stiffness (kPa) and HVPG (r(2) = 0.46, P < 0.001, straight line equation HVPG=7.4 + 0.204*TE). The areas under the ROC curves were 0.80 [95% confidence interval (CI), 0.64-0.97] and 0.80 (95% CI, 0.66-0.94) for the prediction of HVPG ≥ 10 and ≥ 12 mmHg, respectively. Our data suggest that TE can predict the presence of clinically significant and severe PH in HIV/HCV-coinfected patients.

Soluble Fas and Fas ligand in HIV/HCV coinfected patients and impact of HCV therapy.

The aim of this study was to evaluate the influence of clinical and epidemiological characteristics of 183 HIV/HCV coinfected patients and HCV clearance after antiviral treatment on serum sFas and sFasL levels. Thirty out of 183 patients underwent HCV antiviral therapy with IFN-α + RBV for a duration of 48 weeks. HCV genotype 1 and homeostasis model assessment for insulin resistance (HOMA-IR) had a significant positive relationship, and CD4+/µL had a significant negative relationship with sFas (R-square = 0.582; p < 0.001) and sFasL (R-square = 0.216; p < 0.001) in multivariate linear regression analysis. HCV genotype 1 was the only significant variable associated with the sFas/sFasL ratio (R-square = 0.201; p < 0.001). sFas and sFasL levels had positive significant correlations with serum sICAM-1, sVCAM-1, and HOMA levels (p < 0.05). Among patients on IFN-α + RBV therapy, 15 patients showed a sustained virologic response (SVR), while 15 patients were non-responders (NR). Patients with SVR had significant decreases in sFas (p = 0.008) and sFas/sFasL ratio (p = 0.002), while non-responders had a significant increase in sFasL values (p = 0.013). In conclusion, HCV genotype 1, high HOMA, and low CD4+/µL were associated with high serum levels of sFas and sFasL, which indicate higher levels of inflammation and, possibly, increased cardiovascular risk. Moreover, response to HCV antiviral therapy is known to reduce inflammation.

CD81 expression in peripheral blood lymphocytes before and after treatment with interferon and ribavirin in HIV/HCV coinfected patients.

BACKGROUND: CD81 is expressed on lymphocytes and confers HCV viral infectivity support. The aim of our study was to quantify CD81 expression in peripheral blood B- and T-cells of HCV/HIV-coinfected patients and healthy subjects to examine its association with several HCV virological characteristics and the therapeutic responsiveness to HCV antiviral treatment. METHODS: We carried out a cross-sectional study on 122 naïve patients. For a duration of 48 weeks, 24 out of 122 patients underwent HCV antiviral therapy with interferon (IFN)-alpha and ribavirin. T- and B-cell subsets were analysed by flow cytometry. RESULTS: We found that HIV/HCV coinfected patients with HCV-RNA > or =850 000 IU/mL had lower values of %CD19+CD81-CD62L+ and %CD19+CD62L+; and higher values of CD19+CD81+CD62L- and CD19+CD81+ percentages and absolute counts than patients with HCV-RNA <850 000 IU/mL. Similarly, HIV/HCV coinfected patients with the genotype 1 had lower values of %CD19+CD81-CD62L+ and higher values of CD3+CD81+CD62L- and CD3+CD81+ percentages and absolute counts than patients without genotype 1. Moreover, we found that HIV/HCV coinfected patients had higher values of %CD19+HLA-DR+CD25+, %CD19+CD40+CD25+ and %CD19+CD25+ than healthy control patients. When we studied the B- and T-cell subset kinetics of 24 HIV/HCV coinfected patients on HCV antiviral therapy, we found a significant decrease in CD3+CD81+and CD3+CD81+CD62L- subsets and a significant increase in CD3+CD62L+ and CD3+CD81+CD62L+ percentages and absolute counts, but the variation in these markers disappeared several months after stopping the treatment. CONCLUSIONS: We observed a different pattern of CD81 T-cell and B-cell levels in naïve HIV/HCV coinfected patients according to HCV virological status and their subsequent variations during HCV antiviral treatment. CD81 expression might influence HCV pathogenesis and response to HCV antiviral treatment.

Diagnosis of advanced fibrosis in HIV and hepatitis C virus-coinfected patients via a new noninvasive index: the HGM-3 index.

BACKGROUND: Noninvasive tests are increasingly being used for the assessment of liver fibrosis. We aimed to develop a serum index for the identification of advanced fibrosis (F>or=3) in HIV/hepatitis C virus (HCV)-coinfected patients. METHODS: We carried out a cross-sectional study on a group of 195 patients comprised of an estimation group (EG; n=127) and a validation group (VG; n=68) who all underwent liver biopsy and had not received previous interferon therapy. Liver fibrosis was estimated using the METAVIR score. We developed a new serum index (HGM-3) dependent on levels of platelets, alkaline phosphatase, hepatic growth factor, tissue inhibitor of metalloproteinase-1 and hyaluronic acid. RESULTS: In the EG, the area under the receiver operating characteristic curve (AUC-ROC) of HGM-3 for identification of F>or=3 was 0.939 [95% confidence interval (CI) 0.899, 0.979] which was significantly higher than the AUC-ROC of the HGM-2, FIB-4, aspartate aminotransferase to platelet ratio (APRI) and Forns' indexes. With HGM-3 <0.135 for F<3, 57 patients were correctly identified and two patients were misclassified. We found the presence of F<3 with 96.6% certainty. The negative likelihood ratio (LR) was <0.1 and the diagnostic odds ratio (DOR) was >40. With HGM-3 >0.570 in the EG for F>or=3, 31 patients were correctly identified, and five patients were misclassified. We found the presence of F>or=3 with 86.1% certainty. The positive LR was >12 and the DOR was >40. For the VG, the diagnostic accuracy values were similar to the values for the EG. CONCLUSIONS: HGM-3 appears to be an accurate noninvasive method for the diagnosis of bridging fibrosis and cirrhosis in HIV/HCV-coinfected patients.

Comparison of transient elastography and liver biopsy for the assessment of liver fibrosis in HIV/hepatitis C virus-coinfected patients and correlation with noninvasive serum markers.

Transient elastography (FibroScan) is a novel, rapid and noninvasive technique to assess liver fibrosis. Our objective was to compare transient elastography (TE) and other noninvasive serum indexes as alternatives to liver biopsy in HIV/hepatitis C virus (HCV)-coinfected patients. The fibrosis stage (METAVIR Score), TE, the aspartate aminotransferase-to-platelet ratio index, the Forns fibrosis index, FIB-4 and HGM-2 indexes were assessed in 100 patients between January 2007 and January 2008. The diagnostic values were compared by calculating the area under the receiver operating characteristic curves (AUROCs). Using TE, the AUROC (95% CI) of liver stiffness was 0.80 (0.72-0.89) when discriminating between F 2, 0.93 (0.85-1.00) when discriminating between F 3 and 0.99 (0.97-1.00) when discriminating between F or= 3, the AUROCs of TE were significantly higher than those obtained with the other four noninvasive indexes. Based on receiver operating characteristic curves, three cutoff values were chosen to identify F or= 3 (>or=11 kPa) and F4 (>or=14 kPa). Using these best cutoff scores, the negative predictive value and positive predictive value were 81.1% and 70.2% for the diagnosis of F or= 3 and 100% and 57.1% for the diagnosis of F4. Thus, Transient elastography accurately predicted liver fibrosis and outperformed other simple noninvasive indexes in HIV/HCV-coinfected patients. Our data suggest that TE is a helpful tool for guiding therapeutic decisions in clinical practice.

Pegylated interferon {alpha}2a plus ribavirin versus pegylated interferon {alpha}2b plus ribavirin for the treatment of chronic hepatitis C in HIV-infected patients.

OBJECTIVES: The two currently available types of pegylated interferon (peg-IFN) used to treat hepatitis C have different pharmacokinetic properties. It is unclear how these differences affect response to therapy. We compared the effectiveness and safety of peg-IFN-alpha2a and peg-IFN-alpha2b, both with ribavirin, against chronic hepatitis C virus (HCV) infection in HIV-infected patients. METHODS: From the GESIDA HIV/HCV cohort, we analysed patients treated with peg-IFN-alpha2a (n = 315) or peg-IFN-alpha2b (n = 242). The primary endpoint was a sustained virological response (SVR). RESULTS: Both groups were well matched in baseline characteristics except for a higher frequency of injection drug users in the peg-IFN-alpha2b group than in the peg-IFN-alpha2a group (85% versus 76%; P = 0.01) and a higher frequency of bridging fibrosis and cirrhosis (F3-F4) in the peg-IFN-alpha2b group than in the peg-IFN-alpha2a group (42% versus 33%; P = 0.04). End-of-treatment response was significantly lower among patients treated with peg-IFN-alpha2b [40% versus 52%; odds ratio (OR), 1.63; 95% confidence interval (95% CI), 1.16-2.29; P < 0.01]. However, no significant differences were found in SVR between patients treated with peg-IFN-alpha2b and those treated with peg-IFN-alpha2a (31% versus 33%; OR, 1.09; 95% CI, 0.75-1.59; P = 0.655). Therapy was interrupted due to adverse events in 33 (14%) patients treated with peg-IFN-alpha2b and 47 (15%) patients treated with peg-IFN-alpha2a. CONCLUSIONS: No differences in effectiveness and safety were found between peg-IFN-alpha2b and peg-IFN-alpha2a for the treatment of chronic HCV infection in HIV-infected patients.

Inhibition of insulin and somatostatin secretion and stimulation of glucagon release by homologous galanin in perfused rat pancreas.

Results of studies on the effects of exogenous galanin on islet cell secretion are controversial. Until recently, only pig galanin has been available, and structural dissimilarities among the galanin molecules of different species might have contributed to discrepancies among the study results. Thus, we investigated the influence of synthetic rat galanin (50 nM) on unstimulated insulin, glucagon, and somatostatin release and on the responses of these hormones to arginine (10 mM), glucose (16.6 mM), and vasoactive intestinal polypeptide (VIP; 1 nM) in a homologous animal model, the perfused rat pancreas. In addition, the effect of an equimolar concentration of pig galanin on arginine-induced islet cell secretion was examined. Infusion of rat galanin reduced unstimulated insulin release (approximately 60%, P less than 0.01) and the insulin responses to arginine (approximately 30%, P less than 0.025), glucose (100%, P less than 0.01), and VIP (approximately 80%, P less than 0.025). Galanin also inhibited unstimulated somatostatin secretion (approximately 15%, P less than 0.05) and virtually abolished the somatostatin output evoked by arginine, glucose, and VIP. Conversely, rat galanin increased unstimulated glucagon output (approximately 20%, P less than 0.05), potentiated the glucagon response to arginine (approximately 50%, P less than 0.05) and VIP (approximately 90%, P less than 0.05), and counteracted the suppressor effect of glucose on alpha-cell secretion. Pig galanin inhibited the insulin output elicited by arginine (approximately 45%, P less than 0.05) but did not affect the somatostatin and glucagon responses to the aminogenic stimulus. In conclusion, the opposite effects of galanin on insulin and glucagon secretion favor the concept of galanin as a diabetogenic agent. Galanin also behaves as a potent inhibitor of somatostatin release. Finally, the importance of using homologous galanin to study the biological activity of this peptide must be emphasized.

Isoniazid preventive therapy in human immunodeficiency virus-infected persons. Long-term effect on development of tuberculosis and survival.

BACKGROUND: Although the short-term benefit of isoniazid prophylaxis in patients coinfected with human immunodeficiency virus (HIV) and tuberculosis has been shown, long-term benefits are unknown. METHODS: Historical cohort study in an acquired immunodeficiency syndrome unit at a tertiary referral hospital. A sample of 121 HIV-infected patients with positive results on a purified protein derivative test were followed up for development of active tuberculosis and survival. Patients who received isoniazid prophylaxis were compared with patients who did not receive prophylaxis. RESULTS: Of the 121 patients examined, 29 (24%) completed a 9- to 12-month course of isoniazid prophylaxis (median follow-up, 89 months), and 92 (76%) did not receive the drug (median follow-up, 60 months). Active tuberculosis developed in 46 patients (38%). The incidence of tuberculosis was higher among patients with no prophylaxis (9.4 per 100 patient-years) than among patients with isoniazid prophylaxis (1.6 per 100 patient-years) (P = .006). Risk for development of tuberculosis was associated with the absence of isoniazid prophylaxis (relative risk [RR], 6.55; 95% confidence interval [CI], 2.02-21.19). Death during the period of study was more frequent in patients who did not receive isoniazid (50/92 or 54%) than in patients who received isoniazid (7/29 or 24%) (P = .008). Median survival was more than 111 months in patients who received isoniazid compared with 75 months in patients who did not receive isoniazid (P < .001). In a proportional hazards analysis, the development of tuberculosis (RR, 1.88; 95% CI, 1.09-3.27), the absence of isoniazid prophylaxis (RR, 2.68; 95% CI, 1.16-6.17), and a CD4+ cell count lower than 0.20 x 10(9)/L (RR, 3.03; 95% CI, 1.39-6.61) were independently associated with death. Patients who received isoniazid had a longer survival after stratifying for the CD4+ cell count. CONCLUSIONS: Preventive therapy with isoniazid confers long-term protection against tuberculosis and significantly increases survival in patients dually infected with HIV and Mycobacterium tuberculosis.