County-Level Variation in Hepatitis C Virus Mortality and Trends in the United States, 2005-2017.

BACKGROUND AND AIMS: Since 2013, the national hepatitis C virus (HCV) death rate has steadily declined, but this decline has not been quantified or described on a local level. APPROACH AND RESULTS: We estimated county-level HCV death rates and assessed trends in HCV mortality from 2005 to 2013 and from 2013 to 2017. We used mortality data from the National Vital Statistics System and used a Bayesian multivariate space-time conditional autoregressive model to estimate age-standardized HCV death rates from 2005 through 2017 for 3,115 U.S. counties. Additionally, we estimated county-level, age-standardized rates for persons <40 and 40+ years of age. We used log-linear regression models to estimate the average annual percent change in HCV mortality during periods of interest and compared county-level trends with national trends. Nationally, the age-adjusted HCV death rate peaked in 2013 at 5.20 HCV deaths per 100,000 persons (95% credible interval [CI], 5.12, 5.26) before decreasing to 4.34 per 100,000 persons (95% CI, 4.28, 4.41) in 2017 (average annual percent change = -4.69; 95% CI, -5.01, -4.33). County-level rates revealed heterogeneity in HCV mortality (2017 median rate = 3.6; interdecile range, 2.19, 6.77), with the highest rates being concentrated in the West, Southwest, Appalachia, and northern Florida. Between 2013 and 2017, HCV mortality decreased in 80.0% (n = 2,274) of all U.S. counties with a reliable trend estimate, with 25.8% (n = 803) of all counties experiencing a decrease larger than the national decline. CONCLUSIONS: Although many counties have experienced a shift in HCV mortality trends since 2013, the magnitude and composition of that shift have varied by place. These data provide a better understanding of geographic differences in HCV mortality and can be used by local jurisdictions to evaluate HCV mortality in their areas relative to surrounding areas and the nation.

De la hepatitis no-A, no-B hacia la eliminación del virus de la hepatitis C / From the dicovery of non-A, non-B hepatitis virus towards hepatitis C virus elimination

El 5 de octubre de 2020, la Asamblea Nobel y el Comité Nobel de Fisiología o Medicina, anunciaron que tres científicos, los Dres. Harvey Later, Michael Houghton y Charles Rice serían los galardonados con el premio Nobel de Medicina 2020 "por el descubrimiento del virus de la hepatitis C". El virus de la hepatitis C (HCV) en uno de varios virus capaces de causar inflamación crónica del hígado y patologías potencialmente mortales como la cirrosis y carcinoma hepatocelular. Las observaciones del Dr. Harvey Alter en el Centro Clínico de los NIH provocaron el postulado de un virus que era diferente de los virus de la hepatitis A y la hepatitis B conocidos en ese momento. Después de muchos años de frustración tratando de identificar el agente infeccioso responsable del virus asociado a la transfusión no A, no B, utilizando técnicas virológicas convencionales, el Dr. Michael Houghton logró, no solo identificar inequívocamente HCV, sino también generar reactivos esenciales para prevenir la propagación del virus a través de transfusión de lotes de sangre contaminados. Estas herramientas y las herramientas moleculares posteriores que se desarrollaron tras este descubrimiento sugieren que más de 70 millones de personas están actualmente infectadas con HCV en todo el mundo. Tras muchos años de intentos frustrados de aislar y propagar el virus en modelos de cultivo celular para estudiar la virología básica del HCV, el Dr. Charles Rice fue pionero en muchos estudios con el objetivo de caracterizar funciones básicas de las proteínas virales para las que desarrolló, entre otros, sistemas de genética inversa y ensayos funcionales en forma de replicones, una herramienta biológica que fue fundamental para desarrollar las terapias antivirales actuales. Sin embargo, sus experimentos pioneros de genética inversa en el modelo del chimpancé, mediante los cuales rescató viriones infecciosos a partir de material genético viral clonado, aseguraron su presencia entre los premiados. En esta breve revisión, analizamos el contexto en el que se realizaron estas contribuciones fundamentales y cómo se ha impulsado la investigación en el campo hasta el punto en que la OMS sugiere la erradicación del virus utilizando las terapias disponibles actualmente

In october 5 2020, the Nobel Assembly and the Nobel Committee for Physiology or Medicine, announced that three scientists Drs. Harvey Later, Michael Houghton and Charles Rice were the awarded with the Nobel prize in Medicine 2020 "for the discovery of the hepatitis C virus". Hepatitis C virus (HCV) in one of several viruses capable of causing chronic liver inflammation and life-threatening pathologies like cirrhosis and hepatocellular carcinoma. Dr. Harvey Alter observations at the NIH Clinical Center prompted the postulate of a virus that was different from the hepatitis A and hepatitis B viruses known at that time. After many years of frustration trying to identify the infectious agent responsible for the non-A, non-B, transfusion-associated virus using conventional virological techniques, Dr. Michael Houghton succeeded not only at unequivocally identifying HCV, but also at generating essential reagents to prevent the spread of the virus through contaminated blood banks. These tools and subsequent molecular tools develop after this discovery suggest that more than 70 million people are currently infected with HCV worldwide. These studies were followed again by many years of frustrated attempts at isolating and propagating the virus in cell culture models to study basic virology on HCV. Dr. Charles Rice pioneered many studies aiming at characterizing basic functions of the viral proteins for which he developed among others, reverse genetics systems and functional assays in the form of replicons, a biological tool that was instrumental to develop the current antiviral therapies. However, its pioneer reverse genetics experiments in the chimpanzee model, by which he rescued infectious virions from cloned viral genetic material, granted his presence among the awardees. In this brief review, we discuss the context in which these seminal contributions were made and how HCV research has been propelled to the point where WHO is suggesting virus eradication using the currently available therapies

Human Immunodeficiency Virus and Hepatitis C Virus Infection Testing Among Commercially Insured Persons Who Inject Drugs, United States, 2010-2017.

BACKGROUND: We assessed prevalence of testing for human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection among persons who inject drugs (PWID). METHODS: Using a nationwide health insurance database for claims paid during 2010-2017, we identified PWID by using codes from the International Classification of Diseases, Current Procedural Terminology, and National Drug Codes directory. We then estimated the percentage of PWIDs tested for HIV or HCV within 1 year of an index encounter, and we used multivariate logistic regression models to assess demographic and clinical factors associated with testing. RESULTS: Of 844 242 PWIDs, 71 938 (8.5%) were tested for HIV and 65 188 (7.7%) were tested for HCV infections. Missed opportunities were independently associated with being male (odds ratios [ORs]: HIV, 0.50 [95% confidence interval {CI}, 0.49-0.50], P < .001; HCV, 0.66 [95% CI, 0.65-0.72], P < .001), rural residence (ORs: HIV, 0.67 [95% CI, 0.65-0.69], P < .001; HCV, 0.75 [95% CI, 0.73-0.77], P < .001), and receiving services for skin infections or endocarditis (adjusted ORs: HIV, 0.91 [95% CI, 0.87-0.95], P < .001; HCV, 0.90 [95% CI, 0.86-0.95], P < .001). CONCLUSIONS: Approximately 90% of presumed PWIDs missed opportunities for HIV or HCV testing, especially male rural residents with claims for skin infections or endocarditis, commonly associated with injection drug use.

Risk behaviours of homeless people who inject drugs during an outbreak of hepatitis C, Northern Ireland, 2016-2017.

From July to August 2016, 4 homeless people who injected drugs (PWID) with acute or recent hepatitis C virus (HCV) infection were reported in Belfast. A multidisciplinary team including public health, homeless and addiction services undertook an investigation to identify risk behaviours and interrupt transmission chains. Recent HCV cases were defined as negative test within the previous year, or reported injecting for less than 1 year; acute cases had tested negative within the previous 6 months. Contacts in the injecting networks of cases were identified for testing. We undertook a cross-sectional survey using structured questionnaires to elicit risk behaviours for PWID and compare behaviours between self-reported hepatitis C positive and negative subjects. During the outbreak investigation until December 2017, 156 PWID were tested and 45 (29%) cases identified, including 7 (16%) recent and 13 (29%) acute infections. 68 PWID, including 12 cases, were interviewed. All respondents reported using heroin, with 76% injecting once or more daily. Sharing was reported for spoons (58%) and filters (53%), but also needles (27%) and syringes (29%). Hepatitis C positive individuals had higher odds to be injecting in public toilets (AOR 17, 95% CI 0.71-400, P < .05) when compared with hepatitis C negative individuals. Hepatitis C positive individuals were more likely to inject in public spaces, but all respondents indicated concerning risk behaviours. We recommend active surveillance with ongoing testing, expanding existing harm reduction programmes and access to bespoke services.

Tratamentos para hepatite C: da descoberta ao plano de eliminação / Treatments for hepatitis C: from discovery to elimination plan

Revisão bibliográfica acerca da evolução das terapias indicadas para o tratamento da hepatite C, contextualizando com acontecimentos importantes e marcos históricos referentes à história da doença. (AU)

Hepatitis C treatment ­ yesterday, tomorrow and / Therapie der Hepatitis C ­ gestern, heute und

During the last years, treatment of chronic hepatitis C virus infection (HCV) was characterized by the development of new therapeutic agents and their combined use. By now the problem of treating HCV seems to be largely solved. The broad range of available therapeutics has the potential to enable a complete cure of this liver disease, which is associated with many complications, thus providing also economic benefits.

A historical perspective on the discovery and elucidation of the hepatitis B virus.

The discovery in 1965 of the "Australia antigen," subsequently identified as the hepatitis B virus surface antigen (HBsAg), was such a watershed event in virology that it is often thought to mark the beginning of hepatitis research, but it is more accurately seen as a critical breakthrough in a long effort to understand the pathogenesis of infectious hepatitis. A century earlier, Virchow provided an authoritative explanation of "catarrhal jaundice," which did not consider an infectious etiology, but the transmission of jaundice by human serum was clearly identified in two outbreaks in 1885, and the distinction between "infectious" and "serum" hepatitis was recognized by the early 1920s. The inability to culture a virus or reproduce either syndrome in laboratory animals led to numerous studies in human volunteers; by the end of World War II, it was known that the diseases were caused by different filterable agents, and the terms "hepatitis A" and "B" were introduced in 1947 (though some long-incubation cases then designated B must in retrospect have been hepatitis C). The development of a number of liver function tests during the 1950s led to the recognition of anicteric infections and the existence of chronic carriers, but little more could be done until an infectious agent had been identified. Once Blumberg and colleagues had found a specific viral marker, the vast amount of accumulated epidemiologic and clinical data, together with huge numbers of stored serum samples, enabled rapid progress in understanding hepatitis B, and revealed the existence of a vast population of chronically infected people in Asia, Oceania and Africa. In this article, we place the identification of the Australia antigen within the historical context of research on viral hepatitis. Following a chronological review from 1865 to 1965, we summarize how the discovery led to improved safety of blood transfusion, the development of a highly effective vaccine and the eventual identification of the hepatitis C, D and E viruses. This article forms part of a symposium in Antiviral Research on "An unfinished story: from the discovery of the Australia antigen to the development of new curative therapies for chronic hepatitis B."

[The specific enzyme inhibitors for potential therapeutic use]. / Specyficzne inhibitory enzymów o potencjalnym zastosowaniu terapeutycznym.

Therapy for hepatitis C virus (HCV) initially consisted on administering ribavirin - having a broad spectrum of action - and pegylated interferon, and was only effective in 40-50% of patients. Appropriate was to find effective inhibitors of viral replication e.g. by inhibition of a viral enzyme, NTPase/helicase required in the process of translation and RNA replication of the HCV. We developed methods of synthesis of many compounds belonging to different groups - derivatives of nucleosides, benzotriazole, benzimidazole, tropolone and epirubicine. Some of the derivatives inhibit HCV helicase activity at low concentrations and reduces replication of the viral RNA in subgenomic replicon system. In the process of HCV replication casein kinase CK2 plays an important role. It regulates the level of phosphorylation of HCV protein NS5A, which affects the production of infectious virions of HCV. Effective and selective inhibitors of kinase CK2 could be of use in the treatment of HCV in combination with other drugs. CK2 kinase phosphorylates approximately 300 proteins that affect the growth, differentiation, proliferation or apoptosis. Elevated CK2 kinase activity has been observed in several types of cancer and other diseases, therefore, inhibitors of this enzyme are potential therapeutic importance, particularly for anti-cancer treatment. Research carried out in collaboration with prof. Shugar led to the synthesis of one of the most selective inhibitors of this enzyme which is 4,5,6,7-tetrabromo-1H-benzotriazole, used for the study of the role of kinase CK2 in a number of metabolic processes in tumor cells.

Actualización terapéutica en la hepatitis C / Therapeutic update in hepatitis C

La infección por el virus de hepatitis C es un problema de salud que afecta a 130-170 millones de personas en todo el mundo. Aproximadamente un 10-30% de pacientes con hepatitis crónica C progresarán a cirrosis en 20-30 años. El desarrollo de nuevos agentes antivirales de acción directa ha cambiado el manejo de la enfermedad, permitiendo el tratamiento libre de Interferón con eficacia superior a los regímenes terapéuticos previos y mínimos efectos adversos, incluso en algunos subgrupos previamente considerados difíciles de curar como los pacientes cirróticos (AU)

Hepatitis C virus infection is a major health burden affecting 130-170 million people worldwide. Approximately 10-30% of those with chronic hepatitis C will progress to cirrhosis over 20-30 years. The development of new direct-acting antivirals has changed the management of the disease, allowing efficacious Interferon-free therapies superior to prior treatment regimens with minimal side effects, even in some subgroups previously thought to be difficult to cure such as cirrhotic patients (AU)

Transmission of Hepatitis C Virus among Prisoners, Australia, 2005-2012.

Hepatitis C virus (HCV) is predominantly transmitted between persons who inject drugs. For this population, global prevalence of HCV infection is high and incarceration is common and an independent risk factor for HCV acquisition. To explore HCV transmission dynamics in incarcerated populations, we integrated virus sequences with risk behavior and spatiotemporal data and analyzed transmission clusters among prisoners in Australia. We detected 3 clusters of recent HCV transmission consisting of 4 likely in-custody transmission events involving source/recipient pairs located in the same prison at the same time. Of these 4 events, 3 were associated with drug injecting and equipment sharing. Despite a large population of prisoners with chronic HCV, recent transmission events were identified in the prison setting. This ongoing HCV transmission among high-risk prisoners argues for expansion of prevention programs to reduce HCV transmission in prisons.

Emerging epidemic of hepatitis C virus infections among young nonurban persons who inject drugs in the United States, 2006-2012.

BACKGROUND: Reports of acute hepatitis C in young persons in the United States have increased. We examined data from national surveillance and supplemental case follow-up at selected jurisdictions to describe the US epidemiology of hepatitis C virus (HCV) infection among young persons (aged ≤30 years). METHODS: We examined trends in incidence of acute hepatitis C among young persons reported to the Centers for Disease Control and Prevention (CDC) during 2006-2012 by state, county, and urbanicity. Sociodemographic and behavioral characteristics of HCV-infected young persons newly reported from 2011 to 2012 were analyzed from case interviews and provider follow-up at 6 jurisdictions. RESULTS: From 2006 to 2012, reported incidence of acute hepatitis C increased significantly in young persons-13% annually in nonurban counties (P = .003) vs 5% annually in urban counties (P = .028). Thirty (88%) of 34 reporting states observed higher incidence in 2012 than 2006, most noticeably in nonurban counties east of the Mississippi River. Of 1202 newly reported HCV-infected young persons, 52% were female and 85% were white. In 635 interviews, 75% of respondents reported injection drug use. Of respondents reporting drug use, 75% had abused prescription opioids, with first use on average 2.0 years before heroin. CONCLUSIONS: These data indicate an emerging US epidemic of HCV infection among young nonurban persons of predominantly white race. Reported incidence was higher in 2012 than 2006 in at least 30 states, with largest increases in nonurban counties east of the Mississippi River. Prescription opioid abuse at an early age was commonly reported and should be a focus for medical and public health intervention.

Back to the origin of HCV 2c subtype and spreading to the Calabria region (Southern Italy) over the last two centuries: a phylogenetic study.

Circulation of HCV genotype 2 has been described in European Countries where numerous subtypes and unclassified HCV 2 lineages have been reported. In Italy, subtype 1b is the most prevalent, followed by genotype 2. In the present study, phylogeny of HCV 2c was investigated. The phylogeny of HCV 2c isolated from 54 Italian patients in the Calabria region (Southern Italy) was investigated by analyzing a fragment of the NS5B gene. Patients came from 5 metropolitan areas and a small village (Sersale). These areas were geographically dispersed throughout the entire region. A Bayesian coalescent-based framework was used to estimate origin and spreading of HCV 2c in this region. Phylogenetic analysis showed that 28 Italian sequences were intermixed with foreign HCV 2c reference sequences and grouped into 3 major clades: A, B, and C. Nineteen inter-clade sequences were associated uniquely with surgery as risk factor for HCV acquisition. By contrast, a sub-cluster within clade B was associated with blood transfusion. Moreover, sequences from Sersale village grouped in the Italian sub-cluster and were intermixed with 10 sequences from metropolitan areas. The three isolates with the longest branch came from Sersale and belonged to patients who had glass syringes as risk factor. HCV 2c isolates from the Calabria region shared a common ancestor whose origin was traced back to 1889. Our results suggest that, after its introduction - possibly as a result of population movements between Italy and African Countries during Italian colonialism - HCV 2c spread through multiple risk factors, not including intravenous drug use. So, transmission chains followed a pathway different from other European Countries. Although HCV incidence is decreasing, these ways are still ongoing, possibly justifying stability in the relative prevalence of HCV 2c.