Incidence and Clearance of Anal Human Papillomavirus Infection in 16 164 Individuals, According to Human Immunodeficiency Virus Status, Sex, and Male Sexuality: An International Pooled Analysis of 34 Longitudinal Studies.

BACKGROUND: Understanding the natural history of anal high-risk human papillomavirus (hrHPV) infection is key for designing anal cancer prevention programs but has not been systematically characterized. METHODS: We reanalyzed data from 34 studies including 16 164 individuals in 6 risk groups defined by human immunodeficiency virus (HIV) status, sex, and male sexuality: men who have sex with men (MSM) and people with HIV (MSMWH), HIV-negative MSM, women with HIV (WWH), HIV-negative women, men who have sex with women (MSW) with HIV (MSWWH), and HIV-negative MSW. We used Markov models to estimate incidence and clearance of 13 hrHPV types and their determinants. RESULTS: Human papillomavirus (HPV) 16 had the highest incidence-clearance ratio of the hrHPV types. MSMWH had the highest hrHPV incidence (eg, 15.5% newly HPV-16 infected within 2 years), followed by HIV-negative MSM (7.5%), WWH (6.6%), HIV-negative women (2.9%), MSWWH (1.7%), and HIV-negative MSW (0.7%). Determinants of HPV-16 incidence included HIV status and number of sexual partners for MSM, women, and MSW, and anal sex behavior for MSM only. HPV-16 clearance was lower for people with HIV (PWH) and lower for prevalent than incident infection. Among MSM, increasing age was associated with lower clearance of prevalent, but not incident, HPV-16 infection. CONCLUSIONS: This robust and unifying analysis of anal hrHPV natural history is essential to designing and predicting the impact of HPV vaccination and HPV-based screening programs on anal cancer prevention, particularly in MSM and PWH. Importantly, it demonstrates the higher carcinogenic potential of longstanding anal prevalent hrHPV infection than more recent incident infection.

Incidence Rate and Risk Factors for Anal Squamous Cell Carcinoma in a Cohort of People Living With HIV from 2004 to 2017: Implementation of a Screening Program.

BACKGROUND: Anal squamous cell carcinoma is rare, in general, but considerably higher in HIV-infected men who have sex with men. There is no consensus on the screening of at-risk populations. OBJECTIVE: This study aimed to determine the incidence rates of anal squamous cell carcinoma and the efficacy of a screening program. DESIGN: This is a cohort study (SeVIHanal/NCT03713229). SETTING: This study was conducted at an HIV outpatient clinic in Seville, Spain. PATIENTS: From 2004 to 2017, all patients with at least 1 follow-up visit were analyzed (follow-up group), including a subgroup of men who have sex with men who participated in a specialized program for screening and treating anal neoplasia (SCAN group) from 2011 onward. MAIN OUTCOME MEASURES: The primary outcome measure was the incidence rate of anal squamous cell carcinoma. RESULTS: Of the 3878 people living with HIV included in the follow-up group, 897 were transferred to the SCAN group; 1584 (41%) were men who have sex with men. Total follow-up was 29,228 person-years with an overall incidence rate for anal squamous cell carcinoma of 68.4/100,000 person-years (95% CI, 46.7-97.4). The changes in the incidence rate/100,000 person-years (95% CI) over time was 20.7 (3.40-80.5) for 2004 to 2006, 37.3 (13.4-87.3) for 2007 to 2010, and 97.8 (63.8-144.9) for 2011 to 2017 (p < 0.001). The strongest impact on the incidence of anal squamous cell carcinoma was made by the lack of immune restoration (adjusted incidence rate ratio (95% CI): 6.59 (4.24-10); p < 0.001), the Centers for Disease Control and Prevention category C (adjusted incidence rate ratio (95% CI): 7.49 (5.69-9.85); p < 0.001), and non-men who have sex with men (adjusted incidence rate ratio (95% CI): 0.07 (0.05-0.10); p < 0.001) in a Poisson analysis. From 2010 to 2017, incidence rates (95% CI) of anal squamous cell carcinoma within the SCAN group and the men who have sex with men of the follow-up group were 95.7 (39.6-202) and 201 (101-386)/100,000 person-years (adjusted incidence rate ratio (95% CI): 0.30 (0.23-0.39); p<0.001). The incidence rate ratio (95% CI) including non-men who have sex with men in the follow-up group was 0.87 (0.69-1.11); p = 0.269. LIMITATIONS: Adherence to the visits could not be quantified. CONCLUSION: Incidence rates of anal squamous cell carcinoma in people living with HIV increased significantly from 2004 to 2017, especially in men who have sex with men who were not being screened. Participation in the SCAN program significantly reduced the incidence of anal squamous cell carcinoma in men who have sex with men, in whom focus should be placed, especially on those presenting with Centers for Disease Control and Prevention category C and advanced immune suppression. See Video Abstract at http://links.lww.com/DCR/B734. TASA DE INCIDENCIA Y FACTORES DE RIESGO DEL CARCINOMA ANAL A CLULAS ESCAMOSAS EN UNA COHORTE DE PERSONAS QUE VIVEN CON EL VIH DE A IMPLEMENTACIN DE UN PROGRAMA DE DETECCIN: ANTECEDENTES:El carcinoma anal a células escamosas es generalmente raro, pero considerablemente más alto en hombres infectados por el VIH que tienen relaciones sexuales con hombres. No hay consenso sobre el cribado de poblaciones en riesgo.OBJETIVO:Este estudio tuvo como objetivo determinar las tasas de incidencia del carcinoma anal a células escamosas y la eficacia de un programa de detección.DISEÑO:Estudio de cohorte (SeVIHanal / NCT03713229).AJUSTE:Clínica ambulatoria de VIH en Sevilla, España.PACIENTES:De 2004 a 2017, se analizaron todos los pacientes con al menos una visita de seguimiento (grupo F / U), incluido un subgrupo de hombres que tenían relaciones sexuales con hombres que participaron en un programa especializado de cribado y tratamiento de neoplasias anales (SCAN-group) a partir de 2011.PRINCIPALES MEDIDAS DE RESULTADO:Tasas de incidencia del carcinoma anal a células escamosas.RESULTADOS:De las 3878 personas que viven con el VIH incluidas en el grupo F / U, 897 fueron transferidas al grupo SCAN, 1584 (41%) eran hombres que tenían relaciones sexuales con hombres. El seguimiento total fue de 29228 personas-año con una tasa de incidencia general de carcinoma anal a células escamosas de 68,4 / 100000 personas-año [intervalo de confianza del 95%: 46,7-97,4]. El cambio en las tasas de incidencia / 100000 personas-año (intervalo de confianza del 95%) a lo largo del tiempo fue 20,7 (3,40-80,5) para 2004-2006, 37,3 (13,4-87,3) para 2007-2010 y 97,8 (63,8-144,9) para 2011-2017, p <0,001. El impacto más fuerte en la incidencia del carcinoma a células escamosas anal fue la falta de restauración inmunológica [índice de tasa de incidencia ajustado (intervalo de confianza del 95%): 6,59 (4,24-10); p <0,001], categoría C de los Centros de Control de Enfermedades [índice de tasa de incidencia ajustado (intervalo de confianza del 95%): 7,49 (5,69-9,85); p <0,001] y no hombres que tenían relaciones sexuales con hombres [razón de tasa de incidencia ajustada (intervalo de confianza del 95%): 0,07 (0,05-0,10); p <0,001] en el análisis de Poisson. Desde 2010-2017, las tasas de incidencia (intervalo de confianza del 95%) de carcinoma anal a células escamosas dentro del grupo SCAN y los hombres que tienen relaciones sexuales con hombres del grupo F / U fueron 95,7 (39,6-202) y 201 (101- 386) / 100000 personas-año [razón de tasa de incidencia ajustada (intervalo de confianza del 95%): 0,30 (0,23-0,39); p <0,001]. La razón de la tasa de incidencia (intervalo de confianza del 95%), incluidos los no hombres que tenían relaciones sexuales con hombres en F / U, fue de 0,87 [0,69-1,11); p = 0,269].LIMITACIONES:No se pudo cuantificar la adherencia a las visitas.CONCLUSIÓNES:La tasa de incidencia del carcinoma anal a células escamosas en personas que viven con el VIH aumentó significativamente de 2004 a 2017, especialmente en hombres que tenían relaciones sexuales con hombres que no se someten a pruebas de detección. La participación en el programa SCAN redujo significativamente la incidencia de carcinoma anal a células escamosas en hombres que tenían relaciones sexuales con hombres, en quienes se debe prestar una especial atención, sobre todo en aquellos que se presentan en la categoría C de los Centros de Control de Enfermedades con inmunodeficiencia avanzada. Consulte Video Resumen en http://links.lww.com/DCR/B734.

Epidemiology of anal human papillomavirus infection and high-grade squamous intraepithelial lesions in 29 900 men according to HIV status, sexuality, and age: a collaborative pooled analysis of 64 studies.

BACKGROUND: Robust age-specific estimates of anal human papillomavirus (HPV) and high-grade squamous intraepithelial lesions (HSIL) in men can inform anal cancer prevention efforts. We aimed to evaluate the age-specific prevalence of anal HPV, HSIL, and their combination, in men, stratified by HIV status and sexuality. METHODS: We did a systematic review for studies on anal HPV infection in men and a pooled analysis of individual-level data from eligible studies across four groups: HIV-positive men who have sex with men (MSM), HIV-negative MSM, HIV-positive men who have sex with women (MSW), and HIV-negative MSW. Studies were required to inform on type-specific HPV infection (at least HPV16), detected by use of a PCR-based test from anal swabs, HIV status, sexuality (MSM, including those who have sex with men only or also with women, or MSW), and age. Authors of eligible studies with a sample size of 200 participants or more were invited to share deidentified individual-level data on the above four variables. Authors of studies including 40 or more HIV-positive MSW or 40 or more men from Africa (irrespective of HIV status and sexuality) were also invited to share these data. Pooled estimates of anal high-risk HPV (HR-HPV, including HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68), and HSIL or worse (HSIL+), were compared by use of adjusted prevalence ratios (aPRs) from generalised linear models. FINDINGS: The systematic review identified 93 eligible studies, of which 64 contributed data on 29 900 men to the pooled analysis. Among HIV-negative MSW anal HPV16 prevalence was 1·8% (91 of 5190) and HR-HPV prevalence was 6·9% (345 of 5003); among HIV-positive MSW the prevalences were 8·7% (59 of 682) and 26·9% (179 of 666); among HIV-negative MSM they were 13·7% (1455 of 10 617) and 41·2% (3798 of 9215), and among HIV-positive MSM 28·5% (3819 of 13 411) and 74·3% (8765 of 11 803). In HIV-positive MSM, HPV16 prevalence was 5·6% (two of 36) among those age 15-18 years and 28·8% (141 of 490) among those age 23-24 years (ptrend=0·0091); prevalence was 31·7% (1057 of 3337) among those age 25-34 years and 22·8% (451 of 1979) among those age 55 and older (ptrend<0·0001). HPV16 prevalence in HIV-negative MSM was 6·7% (15 of 223) among those age 15-18 and 13·9% (166 of 1192) among those age 23-24 years (ptrend=0·0076); the prevalence plateaued thereafter (ptrend=0·72). Similar age-specific patterns were observed for HR-HPV. No significant differences for HPV16 or HR-HPV were found by age for either HIV-positive or HIV-negative MSW. HSIL+ detection ranged from 7·5% (12 of 160) to 54·5% (61 of 112) in HIV-positive MSM; after adjustment for heterogeneity, HIV was a significant predictor of HSIL+ (aPR 1·54, 95% CI 1·36-1·73), HPV16-positive HSIL+ (1·66, 1·36-2·03), and HSIL+ in HPV16-positive MSM (1·19, 1·04-1·37). Among HPV16-positive MSM, HSIL+ prevalence increased with age. INTERPRETATION: High anal HPV prevalence among young HIV-positive and HIV-negative MSM highlights the benefits of gender-neutral HPV vaccination before sexual activity over catch-up vaccination. HIV-positive MSM are a priority for anal cancer screening research and initiatives targeting HPV16-positive HSIL+. FUNDING: International Agency for Research on Cancer.

Response to a reinforced hepatitis B vaccination scheme in HIV-infected patients under real-life conditions.

BACKGROUND: HIV-infected patients are at risk of hepatitis B virus (HBV) coinfection, however, respond worse to HBV vaccination (HBV-V) than immunocompetent adults. This study aimed to determine the response to reinforced HBV-V in HIV-infected subjects under real-life conditions. METHODS: HIV-infected patients followed at a Spanish University Hospital who were seronegative for HBV and who received three double-doses (40 µL) of HBV-V at 0, 1 and 2 months were included. Response to HBV-V was defined as HBV surface antibody concentration of ≥10 IU/L 1-12 months after the last HBV-V dose. RESULTS: Of 332 patients included in the study, 256 (77.1%) showed response to HBV-V. Median (interquartile range) CD4+/CD8+ ratio among the responders was 0.75 (0.52-1.01) versus 0.61 (0.38-0.84) among the non-responders (p = 0.002). Independent predictors for HBV-V response were: female gender [adjusted odds ratio (AOR): 6.240; 95% confidence interval (95%CI): 1.954-19.925; p = 0.002]; non-smoking [AOR: 2.151; 95%CI: 1.243-3.721; p = 0.006]; a CD4+/CD8+ ratio ≥0.67 [AOR: 2.580; 95%CI: 1.209-5.505; p = 0.014] and baseline HIV-RNA ≤50 copies/mL [AOR: 2.049; 95%CI: 1.098-3.824; p = 0.024]. CONCLUSION: Accelerated administration of three double-doses results in considerable high, however still suboptimal, response rates to HBV-V in HIV-infected patients in the clinical practice. A fourth dose should be considered.

High-risk Human Papilloma Virus Testing Improves Diagnostic Performance to Predict Moderate- to High-grade Anal Intraepithelial Neoplasia in Human Immunodeficiency Virus-infected Men Who Have Sex With Men in Low-to-Absent Cytological Abnormalities.

BACKGROUND: Screening methods for anal squamous intraepithelial lesions (SILs) are suboptimal. We aimed to determine the diagnostic performance of a composite endpoint comprising anal liquid-based cytology (aLBC) and high-risk human papillomavirus (HR-HPV) testing to predict histological high-grade SILs (hHSILs). METHODS: From the SeVIHanal cohort, human immunodeficiency virus (HIV)-infected men who have sex with men (MSM) who had an aLBC with concomitant HR-HPV testing were included. hHSILs were determined by high-resolution anoscopy (HRA)-guided biopsy. RESULTS: A total of 705 visits obtained from 426 patients were included. The prevalence of HR-HPV among aLBC results were 51.9% (133/215) normal, 87.9% (20/232) low-grade SILs (LSILs), and 90.9% (149/164) high-grade SILs; P (linear association) < .001. Low prevalence of hHSILs was only observed for the composite aLBC/HR-HPV testing endpoint "normal/noHR-HPV" (10%) and "LSIL/noHR-HPV" (4%). The prognostic values (95% confidence interval) for HR-HPV to predict hHSILs in normal cytology were positive predictive value (PPV), 29.3% (25.6%-33.3%); negative predictive value (NPV), 90.2% (82.8%-94.7%); sensitivity, 83% (69.2%-92.4%); and specificity, 44.1% (36.4%-51.9%). Corresponding figures for cytologic LSILs were PPV, 39.2% (37.4%-41.1%); NPV, 96.4% (78.9%-99.5%); sensitivity, 98.8% (93.3%-99.9%); and specificity, 17.9% (12.1%-24.9%). A positive interaction and a synergistic effect for the composite endpoint were observed (relative excess risk = 1.50, attributable proportion of histological results to interaction = 0.17, synergy index = 1.24). CONCLUSIONS: HRA should not be indicated in the setting of LSILs/noHR-HPV following aLBC-based screening. In contrast, HIV-infected MSM with normal aLBC/HR-HPV infection should be considered for HRA. CLINICAL TRIALS REGISTRATION: NCT03713229.

High-resolution anoscopy in HIV-infected men: Assessment of the learning curve and factors that improve the performance.

OBJECTIVE: To determine the required learning time for high-resolution anoscopy (HRA)-guided biopsy to detect histological high-risk squamous intraepithelial lesions (hHSIL) and to identify factors that impact on the training process. METHODS: All HIV-infected, screening-naïve men-who-have-sex-with-men who underwent HRA conducted by one single observer from 2010 to 2017 in a Spanish HIV-outpatient clinic were analysed. RESULTS: Eighty-five (14.7%) of the 581 patients included presented hHSIL. The factors associated with the capacity to detect hHSIL [adjusted odds ratio (aOR), 95% confidence interval (95%CI)] were the presence of cytological HSIL (3.04, 1.78-5.21; p < 0.001), infection with high-risk human papilloma virus (HR-HPV) (2.89, 1.38-6.05; p = 0.005), the number of biopsies taken/HRA (aOR: 1.28, 1.07-1.52; p = 0.006) and tobacco smoking (1.75; 1.12-2.73; p = 0.014). Two events independently augmented the detection rate of hHSIL: one single experienced pathologist interpreted biopsies after 409 HRA (2.80, 1.74-4.48; p = 0.035) and the anoscopist underwent an additional training after 536 HRA (2.57, 1.07-6.16; p = 0.035). A learning process could be observed throughout the whole study with stable HR-HPV prevalence. CONCLUSION: The data support the growing evidence that the proposed training volume of 50-200 performances is underestimated. Extensive training of both anoscopist and pathologist is warranted and the development of tools to support the diagnostic performance may be considered.

Boceprevir or Telaprevir Based Triple Therapy against Chronic Hepatitis C in HIV Coinfection: Real-Life Safety and Efficacy.

BACKGROUND AND AIMS: Clinical trials of therapy against chronic hepatitis C virus (HCV) infection including boceprevir (BOC) or telaprevir (TVR) plus pegylated interferon and ribavirin (PR) have reported considerably higher response rates than those achieved with PR alone. This study sought to evaluate the efficacy and safety of triple therapy including BOC or TVR in combination with PR in HIV/HCV-coinfected patients under real-life conditions. METHODS: In a multicentre study conducted in 24 sites throughout five European countries, all HIV/HCV-coinfected patients who initiated a combination of BOC or TVR plus PR and who had at least 60 weeks of follow-up, were analyzed. Sustained virologic response 12 weeks after the scheduled end of therapy date (SVR12) and the rate of discontinuations due to adverse events (AE) were evaluated. RESULTS: Of the 159 subjects included, 127 (79.9%) were male, 45 (34.4%) were treatment-naïve for PR and 60 (45.4%) showed cirrhosis. SVR12 was observed in 31/46 (67.4%) patients treated with BOC and 69/113 (61.1%) patients treated with TVR. Overall discontinuations due to AE rates were 8.7% for BOC and 8% for TVR. Grade 3 or 4 hematological abnormalities were frequently observed; anemia 7%, thrombocytopenia 17.2% and neutropenia 16.4%. CONCLUSION: The efficacy and safety of triple therapy including BOC or TVR plus PR under real-life conditions of use in the HIV/HCV-coinfected population was similar to what is observed in clinical trials. Hematological side effects are frequent but manageable.

A polymorphism linked to RRAS, SCAF1, IRF3 and BCL2L12 genes is associated with cirrhosis in hepatitis C virus carriers.

BACKGROUND & AIMS: Host genetic factors could play a primary role in determining risk for cirrhosis development in HCV-infected patients. The aims of this study were to discover new genetic variants associated with this trait and to replicate some associations formerly reported. METHODS: Three hundred and thirty-seven HCV carriers with available data about liver fibrosis status, who initiated treatment with pegylated interferon plus ribavirin, were included. Of them, 77 (22.85%) were cirrhotic. One hundred and forty-four SNPs from 40 genes related to cholesterol metabolism/transport, sustained viral response to HCV therapy, liver fibrosis, or immune response, were genotyped in all samples. Plink software was used to perform univariate association analyses. The results obtained were adjusted by other parameters related to cirrhosis using multivariate logistic regression models. RESULTS: Only the SNP rs12104272, linked to RRAS, SCAF1, IRF3 and BCL2L12 genes, was associated with cirrhosis. It was observed a higher proportion of rs12104272 A allele carriers in the non-cirrhotic group (60.63%) than in the cirrhotic group (38.15%) (adjusted OR = 0.36, 95% CI = 0.180-0.746, P = 0.006). This effect was stronger in the background of rs12979860 CC genotype of IL28B (adjusted OR = 0.069, 95% CI = 0.014-0.349, P = 0.001). CONCLUSION: The rs12104272 SNP could have clinical value to select those individuals at lower risk for cirrhosis development.

Sustained virological response to pegylated interferon plus ribavirin leads to normalization of liver stiffness in hepatitis C virus-infected patients.

INTRODUCTION: Pegylated interferon plus ribavirin (Peg-IFN/RBV) therapy leads to improvements in liver stiffness measurements (LSM) in hepatitis C virus (HCV)-infected patients. However, the rate of LSM return to normal values in response to Peg-IFN/RBV is unclear. Thus, our aim was to assess the probability and factors associated with LSM normalization in HCV-infected patients receiving Peg-IFN/RBV. METHODS: This prospective observational longitudinal study included 160 HCV-infected patients, 111 (69%) with human immunodeficiency virus and receiving Peg-IFN/RBV, with baseline LSM ≥ 7kPa. The outcome variable was LSM normalization, i.e. a stable decrease in LSM below 7kPa after starting Peg-IFN/RBV. RESULTS: After starting Peg-IFN/RBV, 56 [35%, 95% confidence interval (95% CI): 28-42%] patients showed LSM normalization. The probability of LSM normalization was 21% (95% CI: 13.2-32.4%) at 12 months, and 51.3% (95% CI: 39.9-63.9%) at 24 months after Peg-INF/RBV initiation for individuals with sustained virological response (SVR), and 8.3% (95% CI: 4-16.6%) at 12 months and 11.3% (95% CI: 6-20.7%) at 24 months for those without SVR (p<0.001). For individuals with LSM ≥ 7kPa 24 weeks after the pre-planned end of treatment, LSM normalizations were only observed among those with SVR. Achievement of SVR [Hazard ratio (HR, 95% CI): 6.84 (3.39-13.81)] and lack of baseline cirrhosis [HR (95% CI): 4.17 (1.69-10)] were independently associated with LSM normalization after starting Peg-IFN/RBV. CONCLUSIONS: LSM normalizations during Peg-IFN/RBV treatment are more likely, and occur earlier among patients with SVR. In addition, LSM normalizations continue 24 weeks after the scheduled end of therapy, but only among individuals who reach SVR.

Hepatic safety of efavirenz in HIV/hepatitis C virus-coinfected patients with advanced liver fibrosis.

OBJECTIVE: To assess the frequency of severe liver toxicity in HIV/hepatitis C (HCV)-coinfected patients with advanced liver fibrosis receiving efavirenz (EFV)-based antiretroviral combinations. METHODS: One hundred and eighty-nine previously antiretroviral naïve, HIV/HCV-coinfected patients, who started a regimen including two nucleoside analogues plus EFV, and in whom the presence or absence of advanced liver fibrosis could be established, were retrospectively analyzed. Liver fibrosis was evaluated according to a stepwise algorithm including liver biopsy, transient elastography and FIB-4 index. RESULTS: Fifty-six patients had advanced fibrosis - 25 with cirrhosis - and 133 did not. Three (5.4%) subjects with and 9 (6.8%) (p=0.717) without advanced fibrosis developed grade 3-4 transaminase elevation (TE). Grade 4 total bilirubin elevation was seen in 5 (8.9%) patients with advanced fibrosis and in 1 (0.8%) without it (p=0.003). Liver events led to EFV discontinuation in 10 (5.3%) patients, 6 (10.7%) with and 4 (3%) without advanced fibrosis (p=0.031). CONCLUSIONS: The hepatic tolerability of EFV was good in HIV/HCV-coinfected patients with advanced liver fibrosis. The frequency of grade 3-4 TE was similar to that observed in patients without advanced fibrosis, there was no death attributable to liver failure caused by drug toxicity and the rate of EFV discontinuations due to liver events was low.

Impact of observer experience on the reproducibility of transient elastometry in HIV/HCV co-infected patients.

BACKGROUND: Data on the influence of observer experience on transient elastometry (TE) in hepatitis C virus (HCV) infection are scarce, and there are no data on HCV/HIV co-infected patients. METHODS: TE determination was conducted by an experienced and an inexperienced observer in 93 patients who were divided into three groups according to the chronological order of their attendance. The interobserver variability of TE results was analyzed by the intraclass correlation index (ICC) and the interobserver agreement of the classification of significant fibrosis and cirrhosis by the kappa index. RESULTS: The overall ICC was 0.970 (95% confidence interval [CI] 0.954-0.980). For groups 1, 2, and 3, the ICCs were 0.952 (95% CI 0.901-0.977), 0.966 (95% CI 0.931-0.984), and 0.986 (95% CI 0.971-0.993), respectively. The kappa index for the classification of cirrhosis (cutoff value >or=14.6 kPa) for the three groups was 0.53, 1.00, and 0.91. The use of two cutoff points to exclude (<6 kPa) or diagnose significant fibrosis (>9 kPa) yielded a kappa index of 0.72, 1.00, and 1.00, respectively. CONCLUSIONS: In HIV/HCV co-infected patients, the concordance between an inexperienced and an experienced observer is acceptable after a short instruction period. To maximize this concordance, a training period of 60 measurements should be recommended.

Tea flavanols inhibit cell growth and DNA topoisomerase II activity and induce endoreduplication in cultured Chinese hamster cells.

Tea polyphenols are promising chemopreventive anticancer agents, the properties of which have been studied both in vitro and in vivo, providing evidence that - within this group of compounds - the tea flavanols are able to inhibit carcinogenesis, an effect that in some cases could be correlated with increased cell apoptosis and decreased cell proliferation. Of four main tea flavanols, namely (-)-epigallocatechin-3-gallate (EGCG), (-)-epigallocatechin (EGC), (+)-catechin (CA) and (-)-epicatechin (EC), it was found that EGCG was the most potent to inhibit dose dependently the topoisomerase II (TOPO II) catalytic activity isolated from hamster ovary AA8 cells. In the range of concentrations that caused TOPO II inhibition, a high level of endoreduplication, a rare phenomenon that consists in two successive rounds of DNA replication without intervening mitosis, was observed, while neither micronuclei nor DNA strand breaks (Comet assay) were detected at the same doses. We propose that the anticarcinogenic effect of tea flavanols can be partly explained by their potency and effectiveness to induce endoreduplication. Concerning such an induction, maximum effect seems to require a pyrogallol structure at the B-ring. Additional substitution with a galloylic residue at the C3 hydroxyl group leads to further augmentation of the effect. Thus, we suggest that the chemopreventive properties of tea flavanols can be at least partly due to their ability to interfere with the cell cycle and block cell proliferation at early stages of mitosis.

Long-term ingestion of high flavanol cocoa provides photoprotection against UV-induced erythema and improves skin condition in women.

Dietary antioxidants contribute to endogenous photoprotection and are important for the maintenance of skin health. In the present study, 2 groups of women consumed either a high flavanol (326 mg/d) or low flavanol (27 mg/d) cocoa powder dissolved in 100 mL water for 12 wk. Epicatechin (61 mg/d) and catechin (20 mg/d) were the major flavanol monomers in the high flavanol drink, whereas the low flavanol drink contained 6.6 mg epicatechin and 1.6 mg catechin as the daily dose. Photoprotection and indicators of skin condition were assayed before and during the intervention. Following exposure of selected skin areas to 1.25 x minimal erythemal dose (MED) of radiation from a solar simulator, UV-induced erythema was significantly decreased in the high flavanol group, by 15 and 25%, after 6 and 12 wk of treatment, respectively, whereas no change occurred in the low flavanol group. The ingestion of high flavanol cocoa led to increases in blood flow of cutaneous and subcutaneous tissues, and to increases in skin density and skin hydration. Skin thickness was elevated from 1.11 +/- 0.11 mm at wk 0 to 1.24 +/- 0.13 mm at wk 12; transepidermal water loss was diminished from 8.7 +/- 3.7 to 6.3 +/- 2.2 g/(h x m2) within the same time frame. Neither of these variables was affected in the low flavanol cocoa group. Evaluation of the skin surface showed a significant decrease of skin roughness and scaling in the high flavanol cocoa group compared with those at wk 12. Dietary flavanols from cocoa contribute to endogenous photoprotection, improve dermal blood circulation, and affect cosmetically relevant skin surface and hydration variables.