Comportamiento virológico de pacientes con hepatitis C tratados con antivirales cubanos / Virological behavior of patients with hepatitis C treated with Cuban antivirals

Introducción: el seguimiento virológico de los pacientes con hepatitis C se realiza mediante la determinación cuantitativa del ácido ribonucleico viral por técnicas de biología molecular. Objetivos: evaluar el comportamiento virológico de los pacientes con hepatitis crónica C tratados con antivirales cubanos. Materiales y métodos: se realizó un estudio descriptivo, prospectivo en 45 pacientes con hepatitis crónica C atendidos en Consulta de Hepatología del Hospital Universitario Faustino Pérez, de Matanzas, en el período comprendido entre enero 2014 a diciembre 2017, tratados durante 48 semanas con PEG-heberon y ribavirina. De ellos se analizaron las características basales así como los diferentes tipos de respuesta al tratamiento según resultados virológicos. Resultados: predominaron los pacientes del sexo femenino, menores de 45 años, vírgenes de tratamiento y con cargas virales basales altas. Se alcanzó la respuesta virológica rápida en el 31,1%, la temprana total en el 19,4 %, al final del tratamiento en el 77,1% y la respuesta virológica sostenida en el 59,3%. Entre los respondedores predominaron los rápidos con respuesta virológica sostenida y entre los no respondedores, los nulos. Conclusiones: los estudios cuantitativos de ácido ribonucleico viral son esenciales para el seguimiento de los pacientes con hepatitis C ya que a través de sus determinaciones basales, durante el tratamiento y posterior a este, puede evaluarse la respuesta al tratamiento (AU).

Introduction: the virological follow-up of patients with hepatitis C is made through the quantitative determination of the viral ribonucleic acid using techniques of molecular biology. Objectives: to assess the virological behavior of patients with hepatitis C treated with Cuban antivirals. Materials and methods: a prospective, descriptive study was carried out in 45 patients with hepatitis C who attended the Consultation of Hepatology of the University Hospital "Faustino Pérez", of Matanzas, in the period from January 2014 to December 2017, treated with PEG-eberon and ribavirin for 48 weeks. Their basal characteristics were analyzed and also the different kinds of answer to the treatment according to the virological results. Results: female sex, patients aged less than 45 years old, non-treated before and with high viral loads. The fast virological answer was reached in 31 % of the patients, and the total early answer in 19.4 %; at the end of the treatment in 77.1 %, and the sustained virological answer in 59.3 % of the patients. Among the answering ones predominated the fast with sustained virological answer, and among the non-answering predominated the null ones. Conclusions: quantitative studies of viral ribonucleic acid are essential for the follow-up of patients with hepatitis C, because through their basal determinations, during and after the treatment, the answer to the treatment can be evaluated (AU).

Sofosbuvir and Daclatasvir in Mono-and HIV-coinfected Patients with Recurrent Hepatitis C After Liver Transplant

Abstract: Background and aims. Pegylated interferon (Peg-INF) and ribavirin (RBV) based therapy is suboptimal and poorly tolerated. We evaluated the safety, tolerability and efficacy of a 24-week course of sofosbuvir plus daclatasvir without ribavirin for the treatment of hepatitis C virus (HCV) recurrence after liver transplantation (LT) in both HCV-monoinfected and human immunodeficiency virus (HIV)-HCV coinfected patients. Material and methods. We retrospectively evaluated 22 consecutive adult LT recipients (16 monoinfected and 6 coinfected with HIV) who received a 24-week course of sofosbuvir plus daclatasvir treatment under an international compassionate access program. Results. Most patients were male (86%), with a median age of 58 years (r:58-81y). Median time from LT to treatment onset was 70 months (r: 20-116 m). HCV genotype 1b was the most frequent (45%), 55% had not responded to previous treatment with Peg-INF and RBV and 14% to regiments including first generation protease inhibitors. Fifty-six percent of the patients had histologically proven cirrhosis and 6 had ascites at baseline. All patients completed the 24-week treatment course without significant side effects except for one episode of severe bradicardya, with only minor adjustments in immunosuppressive treatment in some cases. Viral suppression was very rapid with undetectable HCV-RNA in all patients at 12 weeks. All 22 patients achieved a sustained virological response 12 weeks after treatment completion. Conclusion. The combination of sofosbuvir plus daclatasvir without ribavirin is a safe and effective treatment of HCV recurrence after LT in both monoinfected and HIV-coinfected patients, including those with decompensated cirrhosis.

Hepatitis C seroprevalence and correlation between viral load and viral genotype among primary care clients in Mexico

OBJECTIVE: To measure hepatitis C virus (HCV) sero-prevalence, prevalence, hepatitis risk characteristics frequency, and genotype correlation with viral load among clients attending health care clinics. MATERIAL AND METHODS: Venous blood samples from l12 226 consecutive consenting adults were collected from January 2006 through December 2009. HCV antibodies were detected by immunoassay. HCV RNA was detected by qRT-PCR and viral genotype was performed by PCR and LIPA test. RESULTS: The HCV seroprevalence observed was l.5 percent (C.I. 95 percent l.3-l.7), from seropositive individuals 60.9 percent reported previous blood transfusion, 28.3 percent declared to have relatives with cirrhosis, 25.2 percent had tattoos or piercings, and 6.9 percent referred to have used drugs. Male gender and transfusion (p<0.00l) were the most frequent hepatitis risk characteristics in the HCV seropositive group. Among seropositive subjects 48.3 percent presented HCV RNA.The most frequent genotype detected in all geographic areas of Mexico was l (subtype lA, 33 percent; subtype lB, 21.4 percent) followed by genotype 2 (subtype 2A, 8.50 percent). Subjects with genotype 1 had a significant correlation with the highest viral load. CONCLUSIONS: Our results show that nearly half of seropositive individuals are chronically infected. HCV infection has been shown in this study to be an emerging health problem in Mexico.

OBJETIVO: Medir la seroprevalencia y prevalencia del virus de hepatitis C (VHC), la frecuencia de caracteristicas de riesgo y la correlacion genotipica con la carga viral en sujetos asistentes a clinicas de medicina familiar. MATERIAL Y METODOS: muestras de sangre venosa se colectaron de l12 226 adultos, previo consentimiento informado, de enero 2006 hasta diciembre 2009, para la deteccion de anticuerpos contra VHC por ELISA. La deteccion de RNA-VHC y el genotipo viral se realizo mediante qRT-PCR. RESULTADOS: La seroprevalencia de VHC fue l.5 por ciento (C.I. 95 por ciento l.3-l.7), 60.9 por ciento reportaron transfusion sanguinea previa, 28.3 por ciento dijo tener familiares cercanos con cirrosis, 25.2 por ciento tenian tatuajes o piercing y 6.9 por ciento refirio ser usuario de drogas intravenosas. El ser hombre, el antecedente de transfusiones y el uso de drogas (p<0.00l), fueron los factores con mayor frecuencia en el grupo VHC seropositivo. La prevalencia del RNA-VHC en seropositivos fue de 48.3 por ciento. El genotipo mas frecuente en todas las areas geograficas de Mexico fue el l (subtipo lA, 33 por ciento; subtipo lB, 21.4 por ciento) seguido por el genotipo 2 (subtipo 2A, 8.50 por ciento). Se observó una correlación positiva de 51 por ciento con la carga viral más alta y el genotipo viral 1A. CONCLUSIONES: Nuestros resultados muestran que cerca de la mitad de individuos seropositivos están infectados crónicamente. Esta infección debe considerarse como un problema emergente de salud pública en México.

Resposta virológica sustentada em pacientes com co-infecção pelos genótipos 1 e 2 do vírus da hepatite C, com apenas nove semanas de terapêutica antiviral: relato de caso / Sustained virological response in patients with coinfection by hepatitis C virus genotypes 1 and 2, after just nine weeks of antiviral therapy: case report

Relata-se um paciente do sexo masculino com 67 anos e sorologia positiva para o vírus da hepatite C (HCV). Exames moleculares revelaram a presença do RNA do HCV, com carga viral de 2.000 cópias/mL e genótipos 1 e 2. O tratamento foi com alfapeginterferon-2a, 180mcg/semana e ribavirina, 1.000mg/dia. Na quarta semana de tratamento, a carga viral para o HCV era indetectável. Na nona semana, o paciente apresentou hematêmese, piora do quadro de astenia, inapetência e comprometimento do estado geral, quando o tratamento foi descontinuado. O PCR foi negativo após 6 meses e permaneceu assim após um ano. O paciente encontra-se assintomático.

A report of a 67 year-old male patient with positive serology for HCV. PCR revealed the presence of HCV RNA, viral load of 2,000 copies/mL and genotypes 1 and 2. The pacient was treated with peginterferon alfa-2a at 180mcg/week and ribavirin at 1,000mg/day. In week four of treatment, HCV viral load was undetectable. In week nine, the patient developed hematemesis, worsening of asthenia, anorexia and impaired general condition, so the treatment was discontinued. The PCR was negative six months and one year after the cessation of treatment. The patient remains asymptomatic.

¿Qué sabemos de hepatitis en Venezuela? / What is known about hepatitis in Venezuela?

Cada vez es más reconocido el problema de salud pública que representa la Hepatitis Viral Crónica B y C en todo el mundo, no escapando nuestro país a ésta situación. Ambas pueden conducir a largo plazo a cirrosis hepática y aumentar el riesgo de cáncer de hígado. Dado que las hepatitis virales son patologías de origen infecto contagioso, la Sociedad Venezolana de Gastroenterología, llevó a cabo una encuesta a nivel nacional con el objeto de conocer la información que se maneja en la comunidad sobre éstas enfermedades. Para ello se entrevistaron 1.109 personas, de todos los estratos sociales, 581 de sexo femenino y 528 masculinos, con edades comprendidas entre 18 y 70 años en 8 regiones del país. El 51% de la población encuestada reconoce que tiene poca información sobre la enfermedad. El 57.36% de los encuestados no conocía las diferencias entre los distintos tipos de hepatitis. Más del 80% de las personas desconocían como se adquiere la Hepatitis B y la hepatitis C y casi el 60% de la población no sabe cómo prevenirlas. Al preguntar si tomaban algunas medidas para evitar la hepatitis el 80% de la población NO lo hace. Del 20 % que toma alguna previsión sólo el 36% se vacuna. Cuando se interrogó sobre conocimiento del tratamiento, el 67.09% no sabía que se utiliza para ello. El 24.71% de la población encuestada refirió haberse realizado la prueba diagnóstica. En vista de los resultados recogidos es necesario incrementar la educación de las comunidades en relación a todo lo relacionado con la hepatitis viral...

It is increasingly recognized the worldwide public health problem that represents the Chronic Viral Hepatitis B and C; not escaping our country to this situation. Both can lead, in long-term, to liver cirrhosis and increase the risk of liver cancer. Given that viral hepatitis is an infectiouscontagious disease, the Venezuelan Society of Gastroenterology conducted a nationwide survey in order to know the information that communities have about these diseases. The survey was made to 1109 persons, of all social strata, having 581 female and 528 male, aged between 18 and 70 years in 8 regions of the country. 51% of the population surveyed acknowledged having little information about the disease. 57.36% of respondents did not know the differences between different types of hepatitis. Over 80% of people were unaware of how to get the Hepatitis B and Hepatitis C and nearly 60% of the population does not know how to prevent them. When they were asked if they took some measures to prevent hepatitis, 80% of the population answered they did not. Of the 20% that took some sort of provision only 36% were vaccinated. When they were questioned about knowing any treatment, 67.09% did not know what was used to attack hepatitis. 24.71% of the surveyed population said that they had taken a diagnostic test. In view of the results is necessary to increase the education of communities in everything related to viral hepatitis...

Hepatitis C: sexual or intrafamilial transmission? Epidemiological and phylogenetic analysis of hepatitis C virus in 24 infected couples / Hepatite C: transmissão sexual ou intrafamiliar? Análise epidemiológica e filogenética do vírus da hepatite C em 24 casais infectados

The role of sexual or intrafamilial transmission of hepatitis C is controversial. A phylogenetic analysis was performed on the non-structural region 5B of the hepatitis C virus (NS5B-HCV). High percentages of homology (mean of 98.3 percent) were shown between the couples. Twenty (83.3 percent) of the 24 men but only two of the women (8.3 percent) reported having had sexually transmitted diseases during their lives. The risk factors for HCV acquisition were blood transfusion (10 couples), use of illegal injected drugs (17), use of inhalants (15), acupuncture (5) and tattoos (5). The shared use of personal hygiene items included toothbrushes between six couples (25 percent), razor blades between 16 (66.7 percent), nail clippers between 21 (87.5 percent) and manicure pliers between 14 (58.3 percent). The high degree of similarity of the hepatitis C virus genome supports the hypothesis of hepatitis C virus transmission between these couples. The shared use of personal hygiene items suggests the possibility of intrafamilial transmission of infection.

O papel da transmissão sexual ou intrafamiliar da hepatite C é controverso. Foi feita análise filogenética, região não estrutural 5B do vírus da hepatite C (NS5B-HCV). Altas percentagens de homologia com média de 98,3 por cento foi revelada entre os casais. Vinte (83,3 por cento) de 24 homens, contra apenas duas (8,3 por cento) mulheres reportaram doença sexualmente transmisível durante suas vidas. Os fatores de risco para aquisição da doença foram: transfusão de sangue para 10 casais, uso de drogas ilícitas injetáveis para 17, inalatórias para 15, acupuntura em 5 e tatuagens para 5. O compartilhamento de utensílios de higiene pessoal incluem: escova de dente para seis (25 por cento) dos casais, lâmina de barbear para 16 (66,7 por cento), cortador de unhas para 21 (87,5 por cento) e alicate de manicure para 14 (58,3 por cento). O alto grau de similaridade genômica entre os vírus da hepatite C suporta a hipótese de transmissão entre os casais. O uso compartilhado de utensílios de higiene pessoal sugere a possibilidade de transmissão intrafamiliar.

Relationship between serum concetrations of type III procollagen, hyluronic acid and histopathological findings in the liver of HCV-positive blood donors

BACKGROUND: Serologic markers have been proposed for monitoring hepatic fibrosis in chronic liver disease. Among fibrosis markers, type III procollagen (PIIIP) and hyaluronic acid have been studied in these patients. AIM: To evaluate the association between these serum markers with histological findings. METHODS: A prospective cross-sectional study was carried out with HCV-positive blood donors. The studied population included men and women whose age ranged from 18 to 60 years, with elevated liver function tests [ALT levels > 1.5 times the normal value and alterations of two or more of the following: any changes in the levels of ALT, aspartate aminotransferase, conjugated bilirrubin, gammaglobulin, gammaglutamyltranspeptidase, albumin, platelet count; alkaline phosphatase levels >1.5 times the normal value, or prothrombin time below 70 percent and above 60 percent]. Fourty-nine patients were submitted to liver biopsy, blood analysis of PIIIP, hyaluronic acid, besides liver function tests. RESULTS: Liver function tests were not associated with tissular fibrosis, as assessed by ALT (>1.5 times above normal, fibrosis risk=18.8 percent; <1.5 times, 11.8 percent). Elevated PIIIP was correlated with 66.7 percent chance of fibrosis, whereas normal levels, 9.3 percent. Hyaluronic acid, when elevated, gave a chance of 33.3 percent of fibrosis; when normal, 12.5 percent. CONCLUSION: There was no association between liver function tests, hyaluronic acid and fibrosis. However, PIIIP was related with liver fibrosis. Maybe, this marker should be useful to assess fibrosis in patients with chronic hepatitis C.

RACIONAL: Marcadores sorológicos têm sido propostos para monitorar fibrose hepática em doença crônica do fígado. Dentre os marcadores de fibrose, ácido hialurônico e procolágeno tipo III têm sido estudados nestes pacientes. OBJETIVO: Avaliar a associação de marcadores séricos de fibrose com achados histológicos. MÉTODOS: Foi realizado estudo transversal prospectivo em doadores de sangue anti-HCV positivos. A população estudada incluiu homens e mulheres com idade entre 18-60 anos com provas de função hepática alteradas (níveis de alanina aminotransferase >1.5 vezes do normal e alterações de dois ou mais dos seguintes: qualquer alteração nos níveis de alanina aminotransferase, aspartato aminotransferase, bilirrubina conjugada, gamaglobulina, gamaglutamiltranspeptidase, albumina, plaquetas, níveis de fosfatase alcalina >1,5 vezes o valor normal, tempo de protrombina abaixo de 70 por cento e acima de 60 por cento). Quarenta e nove pacientes foram submetidos a biopsia hepática e coleta de sangue para análise de procolágeno tipo III, ácido hialurônico e provas funcionais hepáticas. RESULTADOS: Não houve relação entre elevação de provas de função hepática e a presença de fibrose - ALT (>1,5 vezes acima do normal, risco de fibrose = 18,8 por cento; <1,5 vezes, 11,8 por cento). Procolágeno tipo III elevado foi correlacionado com 66,7 por cento chances de fibrose, enquanto nível normal, 9,3 por cento. Ácido hialurônico, quando elevado, demonstrou chance de 33,3 por cento de fibrose; quando normal, 12.5 por cento. CONCLUSÕES: Não houve associação entre provas de função hepática, ácido hialurônico e fibrose, mas houve entre esta última e procolágeno tipo III. Talvez este marcador possa ser útil para avaliar fibrose em pacientes com hepatite crônica pelo vírus C.

Relationship between diversity of hepatitis C quasispecies and histological severity of liver disease

The aim of this work to assess in the diversity of hepatitis C virus (HCV) quasispecies is related to histological severity and duration of infection in a cohort of untreated patients with an estimated onset of the disease. A total of 27 patients with diagnosis of chronic liver disease and history of blood transfusion (n = 16) or intravenous drug use (IDU) (n = 11) were included. All were anti-HCV positive and had detectable serum drug injection. Patients who consumed drugs for more than 2 years, or were coinfected with HBV or HIV were excluded. History of alcohol intake (> 80 g/day), ALT level and age at infection were recorded. Histological assessment of grading and staging was performed according to knodell score. The quasispecies diversity was investigated by single strand conformation polymorphism (SSCP) target to HVR-E2 region and SSCP pattern was evaluated as a single or multiple bands. The number of quasispecies did not correlate with estimated duration of the disease. Patients who acquired hepatitis C by blood transfusion did not differ in number of bands from patients who were IDU. There was no correlation between the heterogeneity of HCV quasispecies and age, serum ALT, Knodell score, HAI and fibrosis. In clonclusion the quasiespecies diversity of E2 had no correlation with grade and stage of chronic HCV infection and the presence of quasispecies was independent of the duration of the disease.

Hepatitis C: resolver los dilemas

La infección por el virus de la hepatitis C, por uno de esos misterios biológicos de la extraña relación entre el germen y el huésped que todavía somos incapaces de resolver con nuestro precario conocimiento, puede dar lugar a un amplio espectro de expresiones cl ínicas que van desde el curso benigno y asintomatico por años hasta cuadros clínicos catastróficos de enfermedad hepática progresiva con cirrosis y eventualmente hepatocarcinoma primario. Con este curso natural tan complejo finalmente, el pronóstico de los pacientes con hepatitis crónica es dificil de predecir. Lo que podemos afirmar es que la evolución y su expresión morbida dependerá de factores concomitantes del huésped y de caracteristicas propias del virus. Entre los primeros los más importantes para tener en cuenta son: edad de adquisición, uso concomitante de alcohol, sexo, enfermedad viral coexistente y respuesta inmune del huésped, entre los segundos el nivel de viremia, el genotipo del virus y el grado de diversidad viral

Interferon alfa en el tratamiento de la hepatitis cronica C: curso de 24 versus 48 semanas. Resultados de un estudio randomizado / Interferon alfa in the treatment of chronic hepatitis C: course of 24 versus 48 weeks. Results of a randomized trial

The aim of this trial was to investigate if a more prolonged course of interferon (IFN) is able to increase the long-term benefit in patients with chronic hepatitis C. Forty-four patients with active chronic hepatitis and antibodies to HCV were randomly assigned to receive IFN-alfa 2b 3 MU t.i.w. during 24 weeks (group I, n 23) or during 48 weeks (group II, n 21). In the evaluation of results, complete response was considered when the ALT values returned to normality during the treatment; and sustained response, when the ALT values persisted below normal range during at least 6 months post therapy. Histologic changes were compared by using the Histological Activity Index, or Knodell score. Viremia status was evaluated for the study of HCV RNA (by nested-RT-PCR). Results: There were no significant differences between boths groups before treatment, in terms of age, sex, ALT, or histologic findings (11 patients in group I, and 7 in group II had cirrhosis). Complete response was found in 9 patients (39.1 per cent) from group I; in 11 (52.4 per cent) from group II (NS). Basal histologic findings were identified as the only predictive factor of complete and sustained response, by logistic regresion analysis. Considering only noncirrhotic patients, complete response was seen in 58.3 per cent in patients from group I, 71.4 per cent in group II. Sustained response was obtained in 4 patients from group I, (17.4 per cent), 7 from group II (33.3 per cent) (NS). Post IFN liver biopsies were performed in 23 patients (12 from group I, 11 from group II). In group I patients, there were no significant changes. In group II, Knodell score was found to be significantly decreased post IFN (pre IFN, median 10, range 3-15; post IFN, median 6, range 2-14) (p<0.05). HCR RNA was absent in serum during the follow-up post IFN in 2 patients from group I, in 3 from group II. The results of this study show that a 48 weeks course of IFN has a trend to achieve a higher sustained response than the usual regime (but non significant); and it produces a decrease in the histologic activity. The best predicitve factor of positive response was the absence of cirrhosis in our study (although we did not evaluate viral factors, such as genotypes or HCV viremia levels).