HCV-HIV Chronic Coinfection Prevalence in Amazon Region.

Hepatitis C virus (HCV) infection is an important public health problem, especially in areas with a low human development index such as the Amazon region. This study aimed to identify the prevalence and genotypes of HCV among people living with HIV (PLWH), both neglected chronic diseases in the Amazon region. From March 2016 to June 2017, 433 PWLH were attended to at two sexually transmitted infection referral centers in the city of Belém, in the Brazilian state of Pará in the Amazon region. All individuals were submitted to testing via the rapid immunochromatographic assay (RIA) for the qualitative detection of anti-HCV antibodies. Samples with anti-HCV antibodies were evaluated by reverse transcriptase polymerase chain reaction (RT-PCR), and samples with HCV RNA were subjected to nucleotide sequencing and phylogenetic analysis. Three (0.7%) PLWH had anti-HCV antibodies, and only one (0.2%) had HCV RNA (genotype 2); of these, 31 (7.1%) self-declared to have used drugs at least one time, and 12 (2.7%) regularly use injected drugs. One participant was elderly, single, heterosexual, with a history of unprotected sex and multiple sexual partners. This study detected a low prevalence of HCV infection and recorded the presence of HCV genotype 2 for the first time among PLWH in the Brazilian Amazon.

Cohort study: Apparent redundancy of fibrosis assessment in young persons with HCV; development of realistic approaches to break the paradigm.

INTRODUCTION AND OBJECTIVES: Hepatitis C Virus (HCV) is a blood-borne, hepatotropic RNA virus causing both acute and chronic infection. Chronic HCV infection predisposes individuals to liver fibrosis, cirrhosis and hepatocellular carcinoma. Staging of fibrosis prior to treatment to determine either treatment choice or required follow up, is standard practice. However, this often acts as a barrier to treatment initiation. We sought to validate the hypothesis that those individuals; mono-infected with HCV, ≤35 years of age; with no additional hepatic insult were unlikely to have significant fibrosis. METHODS: We performed a retrospective analysis of a Hepatitis C Virus database; with collation of relevant basic demographics including age, sex and baseline Transient Elastography measurements pre-treatment. Additionally, we compared the reliability of biochemical fibrosis scores with corresponding transient elastography scores. RESULTS: Our results support the hypothesis that those individuals with chronic HCV ≤35 years old, with no additional risk for fibrogenesis did not have significant liver fibrosis within our cohort. CONCLUSION: Patients ≤35 years old likely do not necessitate fibrosis assessment prior to Direct Acting Antiviral (DAA) treatment in the absence of other significant risk factors for fibrosis. Given the emerging evidence that DAA treatment results in a significant decrease in all-cause mortality and hepatocellular carcinoma development, treatment of those with chronic HCV represents a global priority.

Virucidal activity of oriental hornet Vespa orientalis venom against hepatitis C virus.

BACKGROUND: Hepatitis C virus (HCV) infection is a major worldwide health problem that can cause liver fibrosis and hepatocellular carcinoma (HCC). The clinical treatment of HCV infection mainly relies on the use of direct-acting antivirals (DAAs) that are usually expensive and have side effects. Therefore, achieving the discovery of more successful agents is always urgent. In this context, antiviral compounds that inhibit viral infections and disease progression with important therapeutic activities have been identified in animal venoms including arthropod toxins. This indicates that arthropod venoms represent a good natural source of promising candidates for new antivirals. METHODS: The antiviral activity of the wasp venom (WV), isolated from the Oriental hornet (Vespa orientalis), was assessed using cell culture technique with human hepatocellular carcinoma-derived cell line (Huh7it-1) and the recombinant strain of HCV genotype 2a (JFH1). RESULTS: The results revealed that WV inhibited HCV infectivity with 50% inhibitory concentration (IC50) of 10 ng/mL, while the 50% cytotoxic concentration (CC50) was 11,000 ng/mL. Time of addition experiment showed that the WV blocked HCV attachment/entry to the cells probably through virucidal effect. On the other hand, the venom showed no inhibitory effect on HCV replication. CONCLUSION: WV can inhibit the entry stage of HCV infection at non-cytotoxic concentrations. Therefore, it could be considered a potential candidate for characterization of natural anti-HCV agents targeting the entry step.

Virucidal activity of oriental hornet Vespa orientalis venom against hepatitis C virus

Background Hepatitis C virus (HCV) infection is a major worldwide health problem that can cause liver fibrosis and hepatocellular carcinoma (HCC). The clinical treatment of HCV infection mainly relies on the use of direct-acting antivirals (DAAs) that are usually expensive and have side effects. Therefore, achieving the discovery of more successful agents is always urgent. In this context, antiviral compounds that inhibit viral infections and disease progression with important therapeutic activities have been identified in animal venoms including arthropod toxins. This indicates that arthropod venoms represent a good natural source of promising candidates for new antivirals. Methods The antiviral activity of the wasp venom (WV), isolated from the Oriental hornet (Vespa orientalis), was assessed using cell culture technique with human hepatocellular carcinoma-derived cell line (Huh7it-1) and the recombinant strain of HCV genotype 2a (JFH1). Results The results revealed that WV inhibited HCV infectivity with 50% inhibitory concentration (IC50) of 10 ng/mL, while the 50% cytotoxic concentration (CC50) was 11,000 ng/mL. Time of addition experiment showed that the WV blocked HCV attachment/entry to the cells probably through virucidal effect. On the other hand, the venom showed no inhibitory effect on HCV replication. Conclusion WV can inhibit the entry stage of HCV infection at non-cytotoxic concentrations. Therefore, it could be considered a potential candidate for characterization of natural anti-HCV agents targeting the entry step.(AU)

Virucidal activity of oriental hornet Vespa orientalis venom against hepatitis C virus

Abstract Background Hepatitis C virus (HCV) infection is a major worldwide health problem that can cause liver fibrosis and hepatocellular carcinoma (HCC). The clinical treatment of HCV infection mainly relies on the use of direct-acting antivirals (DAAs) that are usually expensive and have side effects. Therefore, achieving the discovery of more successful agents is always urgent. In this context, antiviral compounds that inhibit viral infections and disease progression with important therapeutic activities have been identified in animal venoms including arthropod toxins. This indicates that arthropod venoms represent a good natural source of promising candidates for new antivirals. Methods The antiviral activity of the wasp venom (WV), isolated from the Oriental hornet (Vespa orientalis), was assessed using cell culture technique with human hepatocellular carcinoma-derived cell line (Huh7it-1) and the recombinant strain of HCV genotype 2a (JFH1). Results The results revealed that WV inhibited HCV infectivity with 50% inhibitory concentration (IC50) of 10 ng/mL, while the 50% cytotoxic concentration (CC50) was 11,000 ng/mL. Time of addition experiment showed that the WV blocked HCV attachment/entry to the cells probably through virucidal effect. On the other hand, the venom showed no inhibitory effect on HCV replication. Conclusion WV can inhibit the entry stage of HCV infection at non-cytotoxic concentrations. Therefore, it could be considered a potential candidate for characterization of natural anti-HCV agents targeting the entry step.

Resistance Mutations A30K and Y93N Associated with Treatment Failure with Sofosbuvir and Daclatasvir for Hepatitis C Virus Infection Non-Responder Patients: Case Reports.

In Brazil, hepatitis C treatment has been evolving significantly with the licensing of direct-acting antivirals (DAAs). However, viral determinants (amino acid substitutions in hepatitis C virus (HCV) genome and infective genotype) associated with host factors (hepatic condition and prior HCV therapy) might limit the achievement of sustained virologic response (SVR). Here, we described two case reports in which the occurrence of HCV NS5A mutations A30K (subtype 3a) and Y93N (subtype 1a) might have influenced daclatasvir (DCV)/sofosbuvir (SOF) combined therapy non-response. Despite high response rates for DAA combined therapies in Brazil, these case reports stated the importance of an investigation about how to manage a DAA treatment failure since a combination of factors, especially the occurrence of resistance substitutions, could impact a rescue therapy with new available antivirals in clinical routine.

Hepatocellular Carcinoma and Associated Clinical Features in Latino and Caucasian Patients from a Single Center.

INTRODUCTION AND AIM: Hepatocellular carcinoma (HCC) is the most common type of liver cancer in adults and has seen a rapid increase in incidence in the United States. Racial and ethnic differences in HCC incidence have been observed, with Latinos showing the greatest increase over the past four decades, highlighting a concerning health disparity. The goal of the present study was to compare the clinical features at the time of diagnosis of HCC in Latino and Caucasian patients. MATERIAL AND METHODS: We retrospectively screened a total of 556 charts of Latino and Caucasian patients with HCC. RESULTS: The mean age of HCC diagnosis was not significantly different between Latinos and Caucasians, but Latinos presented with higher body mass index (BMI). Rates of hypertension, diabetes, and hyperlipidemia were similar in the two groups. The most common etiology of liver disease was alcohol drinking in Latinos, and chronic hepatitis C in Caucasian patients. Non-Alcoholic Steatohepatitis (NASH) was the associated diagnosis in 8.6% of Latinos and 4.7% of Caucasians. Interestingly, alpha-fetoprotein (AFP) levels at time of diagnosis were higher in Latino patients compared to Caucasians, but this difference was evident only in male patients. Multifocal HCC was slightly more frequent in Latinos, but the two groups had similar cancerous vascular invasion. Latino patients also presented with higher rates of both ascites and hepatic encephalopathy. CONCLUSION: Latino and Caucasian patients with HCC present with a different profile of etiologies, but cancer features appear to be more severe in Latinos.

Mortality and Kidney Transplantation Outcomes Among Hepatitis C Virus-Seropositive Maintenance Dialysis Patients: A Retrospective Cohort Study.

RATIONALE & OBJECTIVE: Hepatitis C virus (HCV) infection is common among maintenance dialysis patients. Few studies have examined both dialysis survival and transplantation outcomes for HCV-seropositive patients because registry data sets lack information for HCV serostatus. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Adult long-term dialysis patients treated by a US national dialysis provider between January 1, 2004, and December 31, 2014. EXPOSURE: HCV antibody serostatus obtained as part of clinical data from a national dialysis provider. OUTCOMES: Mortality on dialysis therapy, entry onto the kidney transplant waiting list, kidney transplantation, and estimated survival benefit from kidney transplantation versus remaining on the waitlist. ANALYTICAL APPROACH: After linking clinical data with data from the Organ Procurement and Transplantation Network, Cox and cause-specific hazards regression were implemented to estimate the associations between HCV seropositivity and mortality, as well as entry onto the kidney transplant waitlist. Cox regression was also used to estimate the survival benefit from transplantation versus dialysis among HCV-seropositive individuals. RESULTS: Among 442,171 dialysis patients, 31,624 (7.2%) were HCV seropositive. HCV seropositivity was associated with a small elevation in the rate of death (adjusted HR [aHR], 1.09; 95% CI, 1.07-1.11) and a substantially lower rate of entry onto the kidney transplant waitlist (subdistribution HR [sHR], 0.67; 95% CI, 0.61-0.74). Once wait-listed, the kidney transplantation rate was not different for HCV-seropositive (sHR 1.10; 95% CI, 0.96-1.27) versus HCV-seronegative patients. HCV-seropositive patients lived longer with transplantation (aHR at 3 years, 0.42; 95% CI, 0.27-0.63). Receiving an HCV-seropositive donor kidney provided a survival advantage at the 2-year posttransplantation time point compared to remaining on dialysis therapy waiting for an HCV-negative kidney. LIMITATIONS: No data for HCV viral load or liver biopsy. CONCLUSIONS: HCV-seropositive patients experience reduced access to the kidney transplantation waitlist despite deriving a substantial survival benefit from transplantation. HCV-seropositive patients should consider foregoing HCV treatment while accepting kidneys from HCV-infected donors to facilitate transplantation and prolong survival.

Aspectos clínicos y epidemiológicos de pacientes con carcinoma hepatocelular en dos centros de referencia de Venezuela / Clinical and epidemiological aspects of patients with hepatocellular carcinoma in two reference centers Venezuela

El carcinoma hepatocelular (CHC) es la neoplasia primaria del hígado más frecuente, constituyendo un problema mundial de salud pública por su alta prevalencia y tasa de mortalidad. Evaluar las características clínicas y epidemiológicas de los pacientes con carcinoma hepatocelular. Estudio de casos consecutivos con revisión retrospectiva de los registros médicos de pacientes con diagnóstico de CHC que acudieron a la consulta de hepatología de dos centros caraqueños entre 1997 y 2011. Se evaluaron características clínicas, epidemiológicas y de estadiaje según Barcelona Clinic Liver Cancer, BCLC. Se incluyó 116 pacientes con diagnóstico de CHC. La edad media fue 61,34 ± 12,02 años, 75% eran hombres y 89,7% de los pacientes tenían cirrosis hepática subyacente, siendo confirmada histológicamente en 33,7%. El 70,7% de los pacientes tenían alguna complicación asociada a hipertensión portal. El virus de la hepatitis C (VHC) constituyó la principal etiología de enfermedad hepática (31%), alcohol (21,6%), virus de la hepatitis B, VHB (14,7%) y enfermedad hepática grasa no alcohólica (14,7%). El hepatocarcinoma fue diagnosticado más frecuentemente en pacientes con cirrosis por HBV 15,56%. El 56% de los casos tenían niveles de alfafetoproteína mayores de 300 ng/ml. El lóbulo derecho fue la localización más frecuente (64,7%) y 79,3% de las lesiones mostraron patrón vascular típico en los estudios radiológicos. El estadio tumoral según los criterios de Barcelona Clinic Liver Cancer (BCLC) fueron estadio C (37,9%) D (25,9%), B (24,1%), A (7,8%) y 0 (2,6%). La infección por HCV es la etiología más frecuente de cirrosis hepática en pacientes con CHC, pero la infección por VHB tiene mayor impacto en términos relativos. El diagnóstico se hace en forma tardía (estadios intermedios o avanzados), siendo necesario intensificar medidas de pesquisa en estos pacientes

The hepatocellular carcinoma (HCC) is the main primary liver neoplasia and is a public health problem in the world due to high prevalence and mortality. Evaluate clinical and epidemiological characteristics in patients with Hepatocellular carcinoma. A retrospective analysis of a prospectively maintained database of 116 patients with diagnosis of HCC in two centers of Caracas between 1997 and 2011 was conducted. We evaluated epidemiological, clinical, biochemical and tumor aspects according to Barcelona Clínic Liver Cancer in patients with HCC. Mean age was 61.34 ± 12.02 years, 75% were male and 89.7% of patients had liver cirrhosis. Portal hypertension complications (ascites, hepatic encephalopathy, esophageal varices) were present in 70.7% of patients. Hepatitis C virus (HCV) was the main etiology of hepatic disease (31%) followed by alcohol (21.6%), hepatitis B virus (14.7%) and non alcoholic steatohepatitis (14.7%). HCC was more frequent in patients with cirrhosis associated to HBV infection. The 56% of patients had alpha-fetoprotein levels higher than 300 ng/ml. The 64.7% of tumors were localized in the right lobe of liver and 79.3% of tumor lesions demonstrated typical pattern in radiologic studies. The most patients had advanced disease according to Barcelona Clinic Liver Cancer (BCLC) staging classification (Stage C, 37.9%; stage D, 25.9%; stage B, 24.1%; stage A, 7.8% and stage 0, 2.6%). HCV infection was main cause of cirrhosis in patients with HCC, but HBV infection had higher impact in these patients. Our study showed that the diagnosis of these patients undergo late and is very important intensify screening measures in patients with liver cirrhosis

Coinfección con los virus VIH-VHC y su evolución clínico-inmunológica / HIV-CHV virus coinfection and its immunological-clinical course

OBJETIVO: Determinar la evolución clinico-inmunológica de pacientes coinfectados con los virus VIH-VHC, atendidos en el Instituto de Medicina Tropical Dr. Pedro Kourí, entre los años 2002-2006. MÉTODOS: Se realizó un estudio de cohorte prospectivo donde fueron incluidos 170 pacientes: 40 coinfectados con los virus VIH-VHC (expuestos) y 130 infectados con el VIH (no expuestos). RESULTADOS: La edad media fue de 33,4 años (34,1 años en los pacientes expuestos y 33,4 en los no expuestos). Predominaron el sexo masculino y el color blanco de la piel (143: 84,1 por ciento y 94: 55,3 por ciento, respectivamente). Los niveles de transaminasas glutamicooxalacética (TGO), glutámico-pirúvica (TGP) y deshidrogenasa láctica (LDH) fueron más elevados en los pacientes coinfectados (p<0,05) que en los monoinfectados. El tiempo medio de diagnóstico del VIH se relacionó de manera significativa con el diagnóstico de VHC y con el SIDA. Hubo menos casos con conteo de CD4+ por debajo de 200 cel/mm³ en los expuestos que en los no expuestos y no existieron diferencias significativas cuando se compararon los grupos según los niveles de CD4+ mayores de 200 cel/mm³. No hubo diferencias significativas entre los valores medios de CD4+ según el tiempo de diagnostico del VIH entre ambos grupos de pacientes. CONCLUSIONES: El daño tisular reflejado por un aumento del nivel de transaminasas (TGO y TGP) y de deshidrogenasa lßctica (LDH) es más elevado en los pacientes infectados con HVC, y la coinfección por el VHC no se relaciona con un mayor deterioro inmunológico ni con un aumento de la frecuencia del SIDA

OBJECTIVE: To determine the immunological-clinical course of HIV-CHV coinfected patients, seen in the Pedro Kourí Tropical Medicine Institute between 2002-2006 years. METHODS: A prospective study was conducted including 170 patients: 40 coinfected with HIV-CHV virus (exposed) and 130 infected by HIV virus (no exposed). RESULTS: The mean age was of 33,4 years (34,1 years in exposed patients and 33,4 in those no exposed). There was predominance of white male sex (143: 84,1 percent and dd94: 55,3 percent, respectively. The glutamic-oxalacetic transaminase (GOT), glutamic-pyruvic (GPT) and lactic dehydrogenase (LDH) levels were higher in coinfected patients (p < 0,05) than those monoinfected. The mean time of HIV diagnosis was significantly related to the C hepatitis virus (CHV) and t AIDS. There were less cases with a CD4+ count under 200 cel/mm3 in those exposed that in those no exposed and there were not significant differences when were compared with the groups according to the DC4+ over 200 cel/mm3. Also, there were not marked differences among the mean values of CD43 according to the HIV diagnosis time among both groups of patients. CONCLUSIONS: The tissue damage reflected by an increase of transaminase levels (GOT and PGT) and of lactic dehydrogenase (LDH) is higher in the C hepatitis virus and the coinfection by CHV it is neither related to the great immunologic deterioration nor an increase of AIDS frequency