Cambios en la dermatoscopia digital en lesiones melanocíticas en 368 pacientes con diagnóstico de síndrome de nevus atípicos y su asociación con el desarrollo de melanoma: estudio de cohorte / Dermoscopic Changes in Melanocytic Lesions in 368 Patients With Atypical Nevus Syndrome and Their Association With Melanoma Incidence: A Cohort Study

Antecedentes y objetivo El síndrome de nevus atípico se ha considerado uno de los factores más importantes para el desarrollo de melanoma. El objetivo de este estudio fue describir los cambios dermatoscópicos de las lesiones melanocíticas en pacientes con diagnóstico de síndrome de nevus atípicos, durante el seguimiento digital en 5 años. Material y métodos Se realizó un estudio retrospectivo de seguimiento a una cohorte de pacientes atendidos en un consultorio particular, especializado en cáncer de piel y mapeo digital corporal, localizado en Medellín (Colombia), entre enero de 2017 y diciembre de 2022. Se analizaron las características dermatoscópicas encontradas y su relación con el diagnóstico de un melanoma. Resultados Se incluyeron 368 pacientes, con una mediana de edad de 43 años RIQ (37-51) de los cuales,187 fueron mujeres. Al finalizar el seguimiento, 222 (60,3%) presentaron red atípica, 163 (44,2%) glóbulos asimétricos, 105 (28,5%) regresión blanco gris, 72 (19,5%) regresión de la lesión, 59 (16%) retículo invertido, 28 (7,6%) pigmento excéntrico asimétrico, 21 (5,7%) proyecciones asimétricas y 8 (2,1%) asimetría en el patrón vascular. A los 60 meses de seguimiento a un 12,2% se les diagnosticó un melanoma. Las áreas blanco-grisáceas, los glóbulos asimétricos, el pigmento excéntrico asimétrico y el retículo invertido fueron las estructuras dermatoscópicas que se relacionaron significativamente con un tiempo menor para la presentación de melanoma (p<0,001, p=0,011, p=0,047 y p=0,001, respectivamente). Conclusiones En conclusión, se encontró que las principales características dermatoscópicas de las lesiones melanocíticas en pacientes con nevus displásicos relacionadas con la progresión a melanoma fueron la aparición de áreas blanco-grisáceas, los glóbulos asimétricos, las manchas asimétricas y el retículo invertido (AU)

Background and objective Atypical nevus syndrome has been described as one of the main risk factors for melanoma. The aim of this study was to analyze dermoscopic changes observed in melanocytic lesions over a follow-up period of 5 years in patients with atypical nevus syndrome. Material and methods We conducted a retrospective follow-up study of a cohort of patients seen at a specialized skin cancer and digital body mapping clinic in Medellin, Colombia, between January 2017 and December 2022. We analyzed the dermoscopic changes observed during this period and explored their association with newly diagnosed melanoma. Results A total of 368 patients (187 women) with a median (interquartile range) age of 43 (37-51) years were included. The dermoscopic features observed at 5 years were an atypical network (222 patients, 60.3%), asymmetric globules (163, 44.2%), white-gray regression areas (105, 28.5%), lesion regression (72, 19.5%), a negative pigment network (59, 16%), asymmetric eccentric pigmentation (28, 7.6%), asymmetric projections (21, 5.7%), and asymmetric vascular patterns (8, 2.1%). Melanoma was diagnosed in 12.2% of patients during follow-up. Features significantly associated with a shorter time to melanoma onset were grayish-white areas (P <.001), asymmetric globules (P=.011), asymmetric eccentric pigmentation (P=.047), and a negative pigment network (P=.001). Conclusions The main dermoscopic features of melanocytic lesions in patients with atypical nevus syndrome associated with progression to melanoma were grayish-white areas, asymmetric globules, asymmetric spots, and a negative pigment network (AU)

[Translated article] Dermoscopic Changes in Melanocytic Lesions in 368 Patients With Atypical Nevus Syndrome and Their Association With Melanoma Incidence: A Cohort Study / Cambios en la dermatoscopia digital en lesiones melanocíticas en 368 pacientes con diagnóstico de síndrome de nevus atípicos y su asociación con el desarrollo de melanoma: estudio de cohorte

Background and objective Atypical nevus syndrome has been described as one of the main risk factors for melanoma. The aim of this study was to analyze dermoscopic changes observed in melanocytic lesions over a follow-up period of 5 years in patients with atypical nevus syndrome. Material and methods We conducted a retrospective follow-up study of a cohort of patients seen at a specialized skin cancer and digital body mapping clinic in Medellin, Colombia, between January 2017 and December 2022. We analyzed the dermoscopic changes observed during this period and explored their association with newly diagnosed melanoma. Results A total of 368 patients (187 women) with a median (interquartile range) age of 43 (37-51) years were included. The dermoscopic features observed at 5 years were an atypical network (222 patients, 60.3%), asymmetric globules (163, 44.2%), white-gray regression areas (105, 28.5%), lesion regression (72, 19.5%), a negative pigment network (59, 16%), asymmetric eccentric pigmentation (28, 7.6%), asymmetric projections (21, 5.7%), and asymmetric vascular patterns (8, 2.1%). Melanoma was diagnosed in 12.2% of patients during follow-up. Features significantly associated with a shorter time to melanoma onset were grayish-white areas (P <.001), asymmetric globules (P=.011), asymmetric eccentric pigmentation (P=.047), and a negative pigment network (P=.001). Conclusions The main dermoscopic features of melanocytic lesions in patients with atypical nevus syndrome associated with progression to melanoma were grayish-white areas, asymmetric globules, asymmetric spots, and a negative pigment network (AU)

Antecedentes y objetivo El síndrome de nevus atípico se ha considerado uno de los factores más importantes para el desarrollo de melanoma. El objetivo de este estudio fue describir los cambios dermatoscópicos de las lesiones melanocíticas en pacientes con diagnóstico de síndrome de nevus atípicos, durante el seguimiento digital en 5 años. Material y métodos Se realizó un estudio retrospectivo de seguimiento a una cohorte de pacientes atendidos en un consultorio particular, especializado en cáncer de piel y mapeo digital corporal, localizado en Medellín (Colombia), entre enero de 2017 y diciembre de 2022. Se analizaron las características dermatoscópicas encontradas y su relación con el diagnóstico de un melanoma. Resultados Se incluyeron 368 pacientes, con una mediana de edad de 43 años RIQ (37-51) de los cuales,187 fueron mujeres. Al finalizar el seguimiento, 222 (60,3%) presentaron red atípica, 163 (44,2%) glóbulos asimétricos, 105 (28,5%) regresión blanco gris, 72 (19,5%) regresión de la lesión, 59 (16%) retículo invertido, 28 (7,6%) pigmento excéntrico asimétrico, 21 (5,7%) proyecciones asimétricas y 8 (2,1%) asimetría en el patrón vascular. A los 60 meses de seguimiento a un 12,2% se les diagnosticó un melanoma. Las áreas blanco-grisáceas, los glóbulos asimétricos, el pigmento excéntrico asimétrico y el retículo invertido fueron las estructuras dermatoscópicas que se relacionaron significativamente con un tiempo menor para la presentación de melanoma (p<0,001, p=0,011, p=0,047 y p=0,001, respectivamente). Conclusiones En conclusión, se encontró que las principales características dermatoscópicas de las lesiones melanocíticas en pacientes con nevus displásicos relacionadas con la progresión a melanoma fueron la aparición de áreas blanco-grisáceas, los glóbulos asimétricos, las manchas asimétricas y el retículo invertido (AU)

Dermoscopic Changes in Melanocytic Lesions in 368 Patients With Atypical Nevus Syndrome and Their Association With Melanoma Incidence: A Cohort Study. / Cambios en la dermatoscopia digital en lesiones melanocíticas en 368 pacientes con diagnóstico de síndrome de nevus atípicos y su asociación con el desarrollo de melanoma: estudio de cohorte.

BACKGROUND AND OBJECTIVE: Atypical nevus syndrome has been described as one of the main risk factors for melanoma. The aim of this study was to analyze dermoscopic changes observed in melanocytic lesions over a follow-up period of 5 years in patients with atypical nevus syndrome. MATERIAL AND METHODS: We conducted a retrospective follow-up study of a cohort of patients seen at a specialized skin cancer and digital body mapping clinic in Medellin, Colombia, between January 2017 and December 2022. We analyzed the dermoscopic changes observed during this period and explored their association with newly diagnosed melanoma. RESULTS: A total of 368 patients (187 women) with a median (interquartile range) age of 43 (37-51) years were included. The dermoscopic features observed at 5 years were an atypical network (222 patients, 60.3%), asymmetric globules (163, 44.2%), white-gray regression areas (105, 28.5%), lesion regression (72, 19.5%), a negative pigment network (59, 16%), asymmetric eccentric pigmentation (28, 7.6%), asymmetric projections (21, 5.7%), and asymmetric vascular patterns (8, 2.1%). Melanoma was diagnosed in 12.2% of patients during follow-up. Features significantly associated with a shorter time to melanoma onset were grayish-white areas (P <.001), asymmetric globules (P=.011), asymmetric eccentric pigmentation (P=.047), and a negative pigment network (P=.001). CONCLUSIONS: The main dermoscopic features of melanocytic lesions in patients with atypical nevus syndrome associated with progression to melanoma were grayish-white areas, asymmetric globules, asymmetric spots, and a negative pigment network.

[Translated article] Dermoscopic Changes in Melanocytic Lesions in 368 Patients With Atypical Nevus Syndrome and Their Association With Melanoma Incidence: A Cohort Study.

BACKGROUND AND OBJECTIVE: Atypical nevus syndrome has been described as one of the main risk factors for melanoma. The aim of this study was to analyze dermoscopic changes observed in melanocytic lesions over a follow-up period of 5 years in patients with atypical nevus syndrome. MATERIAL AND METHODS: We conducted a retrospective follow-up study of a cohort of patients seen at a specialized skin cancer and digital body mapping clinic in Medellin, Colombia, between January 2017 and December 2022. We analyzed the dermoscopic changes observed during this period and explored their association with newly diagnosed melanoma. RESULTS: A total of 368 patients (187 women) with a median (interquartile range) age of 43 (37-51) years were included. The dermoscopic features observed at 5 years were an atypical network (222 patients, 60.3%), asymmetric globules (163, 44.2%), white-gray regression areas (105, 28.5%), lesion regression (72, 19.5%), a negative pigment network (59, 16%), asymmetric eccentric pigmentation (28, 7.6%), asymmetric projections (21, 5.7%), and asymmetric vascular patterns (8, 2.1%). Melanoma was diagnosed in 12.2% of patients during follow-up. Features significantly associated with a shorter time to melanoma onset were grayish-white areas (P<.001), asymmetric globules (P=.011), asymmetric eccentric pigmentation (P=.047), and a negative pigment network (P=.001). CONCLUSIONS: The main dermoscopic features of melanocytic lesions in patients with atypical nevus syndrome associated with progression to melanoma were grayish-white areas, asymmetric globules, asymmetric spots, and a negative pigment network.

Correlation of the virological response to short-term maraviroc monotherapy with standard and deep-sequencing-based genotypic tropism prediction methods.

Genotypic tropism testing methods are emerging as the first step before prescription of the CCR5 antagonist maraviroc (MVC) to HIV-infected patients in Europe. Studies validating genotypic tests have included other active drugs that could have potentially convoluted the effects of MVC. The maraviroc clinical test (MCT) is an in vivo drug sensitivity test based on the virological response to a short-term exposure to MVC monotherapy. Thus, our aim was to compare the results of genotypic tropism testing methods with the short-term virological response to MVC monotherapy. A virological response in the MCT was defined as a ≥ 1-log(10) decrease in HIV RNA or undetectability after 8 days of drug exposure. Seventy-three patients undergoing the MCT were included in this study. We used both standard genotypic methods (n = 73) and deep sequencing (n = 27) on MCT samples at baseline. For the standard methods, the most widely used genotypic algorithms for analyzing the V3 loop sequence, geno2pheno and PSSM, were used. For deep sequencing, the geno2pheno algorithm was used with a false-positive rate cutoff of 3.5. The discordance rates between the standard genotypic methods and the virological response were approximately 20% (including mostly patients without a virological response). Interestingly, these discordance rates were similar to that obtained from deep sequencing (18.5%). The discordance rates between the genotypic methods (tropism assays predictive of the use of the CCR5 coreceptor) and the MCT (in vivo MVC sensitivity assay) indicate that the algorithms used by genotypic methods are still not sufficiently optimized.

[Characteristics of metastatic prostate cancer occurring in patients under 50 years of age]. / Patrón de presentación del cáncer de próstata avanzado en pacientes menores de cincuenta años.

OBJECTIVE: To identify the clinical features, diagnostic approach, and treatment of metastatic prostate cancer in young adult patients. METHODS: A retrospective review was made of the clinical histories of patients under 50 years of age diagnosed with prostate cancer at the urology department of the National Institute for Neoplastic Diseases from 1952 to 2005. Demographic characteristics and data on history, symptoms, diagnostic procedures, treatment, and disease course were collected. Data were statistically analyzed and compared to information obtained from a literature search. RESULTS: There were 69 patients aged less than 50 years who had been diagnosed with prostate cancer, 60% of whom had metastatic tumors. Mean patient age was 45.5 years, with a lower range of 29. All patients reported bone pain, associated to other signs and symptoms such as spinal cord compression (19.5%), lower limb edema (17%), peripheral adenopathies (36.5%), and abdominal tumor (2.4%). All patients had bone metastases, of which 14.6% were in solid organs (lung and liver), 48.7% in retroperitoneum, and 7.3% in mediastinum. Initially, three patients were diagnosed a lymphoproliferative syndrome, one patient a retroperitoneal tumor of unknown etiology, and four patients a metastasis from an unknown primary tumor. Mean prostate-specific antigen (PSA) level was 795 ng/mL (3-6500). All pathologies were reported as poorly differentiated or undifferentiated. Mean survival was 16.1 months (1-84), and all patients died due to disease progression. CONCLUSIONS: Advanced prostate cancer is an uncommon condition in young adults. Its clinical presentation is atypical, as metastases may mimic other diseases. The course of disease is indolent, and prognosis is poor. In patients with risk factors, PSA testing should be started before 50 years of age.

Glycogen synthase kinase-3 is involved in the regulation of the cell cycle in cerebellar granule cells.

Recent studies have demonstrated that neuronal reentry in the cell cycle and specifically the expression of the transcription factor E2F-1, constitutes a pathway that may be involved in neuronal apoptosis after serum and potassium withdrawal. Other enzymes such as glycogen synthase kinase-3beta (GSK-3beta) are also involved in this apoptotic stimulus, and thus in the process of neuronal cell death. Primary cerebellar granule cells (CGNs) were used in this study to determine whether pharmacological inhibition of GSK-3beta is involved in neuronal modulation of the cell cycle, and specifically in the regulation of E2F-1 and retinoblastoma protein (Rb). CGNs showed a dramatic increase in GSK-3beta activity after 2h of serum and potassium deprivation. Immunoblot and activity assays revealed that lithium and SB415286 inhibit fully the activation of GSK-3beta and attenuate the expression of cyclin D, cyclin E, pRb phosphorylation and the transcription factor E2F-1. These data were confirmed using AR-014418, a selective GSK-3beta inhibitor that prevents the expression of cell-cycle proteins. Our data indicate that GSK-3beta inhibition regulates, in part, the cell cycle in CGNs by inhibiting Rb phosphorylation and thus inhibiting E2F-1 activity. However, the selective inhibition of GSK-3beta with AR-A014418 had not effect on cell viability or apoptosis mediated by S/K withdrawal. Furthermore, our results suggest that selective GSK-3beta inhibition is not sufficient to protect against apoptosis in this S/K withdrawal model, indicating that Li(+) and SB415286 neuroprotective effects are mediated by the inhibition of additional targets to GSK3beta. Therefore, there is a connection between cell cycle and GSK-3beta activation and that these, along with other mechanisms, are involved in the molecular paths leading to the apoptotic process of rat CGNs triggered by S/K withdrawal.

Influence of hepatitis C and hepatitis G virus co-infection on viral and cellular dynamics in patients infected with human immunodeficiency virus following interruption of highly active anti-retroviral therapy.

This study describes the influence of hepatitis C virus (HCV) and hepatitis G virus (HGV) co-infection on CD4 cell count decline and plasma human immunodeficiency virus (HIV) viral load in HIV-infected patients during a 1-year period following interruption of highly active anti-retroviral therapy (HAART) guided by CD4 count. CD4 cell count decline and plasma HIV viral load did not differ between HIV mono-infected patients and those patients co-infected with HCV and HGV. HCV genotype 1 had no apparent influence on the cellular and viral dynamics in HIV-infected patients compared with other HCV genotypes, although the unbalanced groups make larger studies desirable.

Analysis of quasispecies in the viral 5' untranslated region of hepatitis C virus to evaluate ribavirin mutagenic effect in patients receiving ribavirin and interferon-alfa.

In the study presented here the ribavirin mutagenic effect was investigated by analyzing quasispecies in the viral 5' untranslated region of hepatitis C virus in six patients with chronic infection who started interpheron-alpha and ribavirin therapy. A remarkable mutation rate during treatment was found in only one individual. This patient had a sustained response and harbored a type 3a virus strain. The different mutated clones in this patient demonstrated no apparent close relationship that could suggest lack of selection pressure by ribavirin. The mutations were located within the loops of subdomains IIIb and IIId of the internal ribosomal entry site. This is an interesting initial finding that needs to be substantiated in a larger trial.

Desarrollo de un instrumento de evaluacion de las practicas clinicas de los estudiantes de enfermeria / Development of a tool for assessing clinical practice in nursing students

Objetivo. Validacion de un instrumento de evaluacion del aprendizaje de los estudiantes de enfermeria durante sus practicas clinicas. Material y metodos. Se elaboraron 132 preguntas capaces de medir conocimientos, habilidades y actitudes, de las que 22 expertos evaluaron supertinencia y claridad mediante la tecnica de Delphi. Se seleccionaron 65 preguntas de (..) (AU)

Objective. Validation of a tool for assessment of nursing students learning during their clinical practice. Material and methods. One hundred thirty-two questions elaborated to measure knowledge, skills and attitudes, were rated by 22 judges to assess their pertinence and clarity through Delphi technique. As a result, 65 questions regarding hospital nursing were finally selected and administered to 194 students of the three academic courses. Results. Factorial analysis provided nine dimensions, which internal consistency, measured by Cronbach¡s alpha, ranged between 0.63 and 0.97. The overall scale gave an intraclass correlation of 0.89 in the test-retest reliability and 0.62 in the inter-raterreliability. Several dimensions correlated positively with the dimensions of responsibility, cautiousness and vigour from the Gordon Personal Profile Inventory. A reduced scale with 23 items correlated with the overall scale (intraclass correlation: 0.98).Conclusions. This measurement tool shows face and construct validity and good internal and intrarater consistency. The small inter-rater reliability would require raters to be specifically trained (AU)

HIV-1 plasma viremia not increased in patients receiving highly active antiretroviral therapy after influenza vaccination.

The effect of vaccinating patients with sustained undetectable HIV-1 viremia (VL) achieved with highly active antiretroviral therapy was prospectively investigated. During the 1998 influenza immunization period, 39 HIV-1-infected patients who showed a VL<20 copies/ml for at least 6 months before the study entry date were vaccinated for influenza. Twenty-two vaccinees were immunized at entry. Seventeen controls were followed for 4 weeks after entry, crossing over then to the vaccination group. The proportion of patients with undetectable VL was not significantly different between the vaccination and control groups 2 and 4 weeks after entry. Therefore, influenza immunization of patients with undetectable viremia achieved with highly active antiretroviral therapy does not seem to affect VL.

Minimal liver injury in chronic hepatitis C virus infection is associated with low levels of soluble TNF-alpha/Fas receptors and acquisition in childhood.

BACKGROUND/AIMS: The rate of progression to cirrhosis of chronic hepatitis C might be related to an upregulation of TNF-alpha/Fas pathways. METHODS: The serum levels of soluble TNF-alpha type II receptor (sTNFr-II) and soluble Fas antigen (sFas) were analyzed in patients with different histological outcomes of chronic parenterally acquired HCV infection of similar duration. RESULTS: One hundred and forty-five HCV-infected patients had a known duration of infection. Twelve (8.3%) patients had minimal changes and were assigned to the case group. The control group was selected from the 24 (17%) patients with cirrhosis and the 54 (37%) with chronic active hepatitis (CAH). Two controls, one with CAH and one with cirrhosis, were paired with the cases following these criteria: duration of infection, transmission route and sex. The proportions of genotype 1b and HCV RNA serum levels were similar among the groups. The median serum levels of sTNFr-II and sFas were significantly lower in the case group than in the control groups. The cases were significantly younger when they became infected than the control groups. Indeed, most cases were infected within the first 10 years of life. sTNFr-II and age at infection were independently associated with the minimal injury case group. When sTNFr-II was excluded from the logistic regression model, sFas and age at infection were independently associated with the case group. CONCLUSION: The rate of progression of parenterally acquired chronic hepatitis C to end-stage liver disease might be related to an upregulation of the TNF-alpha/Fas pathways and an age-dependent host response.

Influence of hepatitis C virus infection on the mortality of antiretroviral-treated patients with HIV disease.

The aims of this study were to analyze the mortality directly attributable to chronic viral hepatitis in HIV-1 infected patients and to investigate the influence of hepatitis virus infections on the survival of this population. A cohort of 328 HIV-1 infected, antiretroviral-treated patients, followed up from 1989 to 1996, was investigated in the study. The median follow-up period of the cohort was 120 weeks. The median baseline CD4 + cell count of the cohort was 303 cells/mm3. Hepatitis C virus, hepatitis B virus and hepatitis D virus infections were present in 214 (65%), 16 (4.9%) and 9 (2.7%) patients, respectively. Sixty-seven (20.4%) subjects died but there was no information on the vital status of 36 patients (11%). The causes of mortality were AIDS in 49 (73%), liver failure in 3 (4.5%) and other causes in 15 (22.4%). The cohort was divided into two groups for survival analysis, the groups consisting of persons infected by a hepatitis virus and persons without hepatitis virus infection. There was no difference in survival between the two groups (p = 0.31, log-rank). It is concluded that mortality among HIV-1/hepatitis virus coinfected patients with moderate to severe immunosuppression is mostly due to AIDS, and that the survival of these subjects is not influenced by the presence of hepatitis virus infections, particularly hepatitis C virus.

Unexpected high prevalence of hepatitis C virus genotype 4 in Southern Spain.

BACKGROUND/AIMS: A unusually high rate of HCV-infected individuals in whom the HCV genotype cannot be ascertained by means of single PCR and LIPA procedures has recently been reported in our area. The aim of the present study was to investigate the epidemiological, clinical and molecular characteristics of these patients. METHODS: Cross-sectional study. Eighty anti-HCV-positive patients with chronic liver disease, 45 (56.25%) of them intravenous drug users, were included. HCV genotyping was carried out in all patients using commercial single PCR and LIPA procedures. Samples where no HCV RNA amplification and/or indeterminate HCV genotype were found were also tested by means of a nested PCR. HCV viral load was measured in all patients. RESULTS: HCV genotyping was not achieved in 23 (28.75%) individuals. No amplification of HCV RNA was found in 19 of them, and in four other cases the LIPA procedure did not allow identification of a distinct HCV genotype. After the use of nested PCR+LIPA, it was found that the HCV genotype 4 was found in 11 of those 23 individuals (47.82%). Ten of these 11 HCV genotype 4-harboring individuals were intravenous drug users. The HCV viral load was lower in HCV genotype 4-harboring individuals than in those whom the genotypes 1, 2 or 3 were found (p<0.001). CONCLUSIONS: A high rate of HCV genotype 4-harboring cases has been found among HCV-infected individuals in Southern Spain. Had only single PCR been used, these individuals could have been wrongly regarded as non-viremic.

Human immunodeficiency virus infection modifies the natural history of chronic parenterally-acquired hepatitis C with an unusually rapid progression to cirrhosis.

BACKGROUND/AIMS: To investigate the possible role of HIV infection in the natural history of chronic parenterally-acquired hepatitis C. METHODS: A multicenter cross-sectional study was performed in 547 patients with chronic parenterally-acquired hepatitis C with or without HIV infection (116 HIV-positive and 431 HIV-negative). Approximate duration of HCV infection was estimated in all patients included, and histologic diagnoses made at different time intervals following HCV infection were analyzed in both groups. Factors related to serum HCV-RNA levels were also investigated. RESULTS: Histologic findings were similar in liver biopsies from both HIV-infected and noninfected patients. However, in the first 10 years, 13 out of 87 (14.9%) HIV-positive subjects developed cirrhosis, in comparison with 7 out of 272 (2.6%) in the HIV-negative group (p < 0.01). Similar results were found in the first 5 and 15 years, respectively, and most of the HIV-negative patients with cirrhosis (42 out of 56) developed cirrhosis in a time interval longer than 15 years. Consequently, mean interval from estimated time of HCV infection to cirrhosis was significantly longer in HIV-negative than HIV-positive patients (23.2 vs. 6.9 years; p < 0.001). Chronic active hepatitis (with and without cirrhosis) and long duration of HCV infection were significantly associated with higher HCV load (p < 0.05). Finally, HIV-positive patients with CD4+ cell counts > 500 cells/ml showed a lower HCV load than those with < 500 cells/ml (p < 0.05). CONCLUSIONS: HIV infection modifies the natural history of chronic parenterally-acquired hepatitis C with an unusually rapid progression to cirrhosis. HIV-related immunodeficiency may be a determinant of higher hepatitis C viremia levels and more severe liver damage.

Influence of human immunodeficiency virus type 1 infection on the natural course of chronic parenterally acquired hepatitis C.

The aim of the present study was to investigate the possible role of human immunodeficiency virus (HIV) infection in the natural course of chronic hepatitis C. Seventy-six adult patients with chronic parenterally acquired hepatitis C virus (HCV) infection examined from 1989 to 1993 were enrolled; of these 32 (42.1%) were HIV positive and 44 (57.9%) were HIV negative. Serum HCV RNA quantitation was carried out by polymerase chain reaction in a well-characterized group (n = 20; 11 HIV positive and 9 HIV negative). Distribution of histological findings in liver biopsies from both HIV-infected and noninfected patients was similar. However, within 15 years after initial HCV infection, 8 of 32 (25%) HIV-positive patients developed cirrhosis, in comparison with only 2 of 31 (6.5%) patients in the HIV-negative group (p < 0.05); similar incidences of cirrhosis were found in both patient groups within 5 and 10 years after HCV infection. Most of the HIV-negative cirrhotic patients (9 of 11) developed cirrhosis in a time interval longer than 15 years. Finally, HCV load was almost ten times higher (1 10-fold dilution) in the HIV-positive group, but this difference did not reach statistical significance in this small study population. These results suggest that HIV infection can alter the natural course of chronic parenterally acquired hepatitis C, causing an unusually rapid progression to cirrhosis.

High rate of nonspecific anti-hepatitis C reactivity amongst homosexual men in comparison with that found in other sexually active groups and blood donors. Viral Hepatitis and AIDS Study Group.

OBJECTIVES: To investigate the concordance of anti-hepatitis C virus (anti-HCV) reactivity by a second-generation enzyme immunoassay (EIA-2) and by a four-antigen recombinant immunoblot assay (4-RIBA) in homosexual men, in comparison with that found in other sexually active groups and blood donors. DESIGN: Prospective study. SETTING: Tertiary referral centre, Seville, Spain. SUBJECTS: A total of 1203 subjects were studied. Eight hundred and three were sexually active individuals: 547 female prostitutes, 88 heterosexual men who had frequent sexual intercourse with prostitutes, and 168 homosexual men. All of them denied blood transfusion and parenteral drug use. In addition, 400 voluntary blood donors were selected at random. MAIN OUTCOME MEASURES: All serum samples were screened for anti-HCV by EIA-2 and repeatedly reactive sera were tested by 4-RIBA. Homosexual men were also screened for anti-human immunodeficiency virus (anti-HIV), hepatitis B virus (HBV) markers and gammaglobulin concentration. Finally, serum samples from homosexual men reactive for anti-HCV by EIA-2 were analyzed for HCV-RNA by polymerase chain reaction (PCR). RESULTS: Concordance between EIA-2 and 4-RIBA in female prostitutes (71.4%), clients of prostitutes (75.0%), and blood donors (83.3%) was significantly higher than in homosexual men (38.8%) (P < 0.04). In this collective the concordance between 4-RIBA and PCR was 85.7% for positive cases and 88.8% for negative ones, and EIA-2 ratios in reactive sera were significantly higher in 4-RIBA confirmed cases (P < 0.0001). No correlation between false positive EIA-2 results and presence of HIV infection, HBV markers or hypergammaglobulinaemia was found in homosexual men by univariate analysis. CONCLUSIONS: There is a high level of non-specific anti-HCV reactivity by EIA-2 amongst homosexual men in comparison with that found in other sexually active groups and blood donors. The true prevalence of HCV infection amongst homosexual men could be even lower than previously described.

Predictive value of IgM antibodies to hepatitis C virus in patients with chronic hepatitis C undergoing interferon-alpha therapy. Analysis by two different methods.

To determine the predictive value of IgM anti-hepatitis C virus (HCV) testing in patients with chronic hepatitis C infections undergoing interferon-alpha (IFN-alpha) therapy, IgM anti-HCV reactivity was analysed by two different methods (non-commercial and commercial) in 19 patients and monitored at times 0 (pretreatment), 3, 6, 12, and 24 months during follow-up. Eight patients were non-responders, five remained in sustained response 1 year after stopping treatment, and six had a relapse. No correlation between alanine transaminase (ALT) levels and IgM anti-HCV reactivity was found by either method in baseline samples. In addition, neither the presence nor absence of IgM anti-HCV in baseline samples, nor the loss of specific IgM reactivity during treatment, had any predictive value. Finally, no other parameters analysed (age, sex, risk group and histological diagnosis), were significantly associated with IgM anti-HCV reactivity in our study. In summary, these results suggest that baseline detection and monitoring of IgM anti-HCV reactivity are not useful in predicting the sustained response to IFN-alpha therapy in chronic hepatitis C infection.

Hepatitis C virus infection among sexually promiscuous groups and the heterosexual partners of hepatitis C virus infected index cases.

To define the role of sexual transmission in the spread of hepatitis C virus (HCV) infection, a seroprevalence study of antibodies against HCV was performed in populations at high risk for sexually transmitted diseases. Subjects included 310 female prostitutes, 88 clients of prostitutes, 168 homosexual men and 147 stable heterosexual partners of index cases reactive for anti-HCV (98 of whom were partners of drug addicts coinfected with HCV and human immunodeficiency virus [HIV]). All subjects denied prior transfusion or intravenous drug use. Controls were 400 voluntary blood donors selected randomly from first-time donors. The prevalence of anti-HCV by enzyme immunoassay, confirmed by a second-generation recombinant immunoblot assay, was 6.4% in prostitutes, 6.8% in clients of prostitutes, 4.2% in homosexual men, 7.4% in heterosexual partners of index cases and 1.2% in random donors. However, the anti-HCV prevalence in stable heterosexual partners of HCV-positive/HIV-positive index cases was 2.2 times higher than in stable heterosexual partners of index cases reactive for anti-HCV only (9.2% vs. 4.1%), and sexual partners of index cases coinfected with HCV and HIV were almost three times more likely to be infected with HIV than with HCV (25.5% vs. 9.2%). These data suggest that HCV infection may be sexually transmitted but with low efficiency and that this efficiency could be increased in the presence of coexistent HIV infection in the index case.

Hepatitis B virus occult infection in subjects with persistent isolated anti-HBc reactivity.

The aim of this study was to investigate the presence of hepatitis B virus occult infection in asymptomatic subjects with persistent anti-HBc reactivity but no other hepatitis B virus serological markers, including HBsAg, anti-HBs, IgM anti-HBc and HBV-DNA. For this purpose we used both polymerase chain reaction assays in sera and immunohistochemistry for HBsAg and HBcAg in liver biopsy specimens. Twenty-four cases were studied: 15 were drug abusers or homosexuals (eight with normal alanine aminotransferase levels) and nine were heterosexuals with raised alanine aminotransferase levels (> 45 U/l) but with no history of blood transfusion or ethanol intake (< 80 g daily). In all but five cases, liver biopsy was performed in subjects with persistent elevated alanine aminotransferase levels. In 10 out of 24 cases (41.66%) hepatitis B virus infection was demonstrated by polymerase chain reaction or immunohistochemistry, and when results from both procedures were available (n = 11) hepatitis B virus infection was detected in 63.63% of the subjects. The only clinical feature associated with HBV infection was the presence of persistent elevated alanine aminotransferase levels (p < 0.05). In conclusion, persistent isolated anti-HBc reactivity may be a relatively common serologic pattern for hepatitis B virus occult infection, at least in patients with chronic liver disease.