Routes of Infection, Viremia, and Liver Disease in Blood Donors Found to Have Hepatitis C Virus Infection

Conry‐Cantilena, Cathy; VanRaden, Mark; Gibble, Joan; Melpolder, Jacqueline C.; Shakil, AO; Viladomiu, L; Cheung, Ling; DiBisceglie, Adrian M.; Hoofnagle, Jay H.; Shih, Jennifer

doi:10.1056/nejm199606273342602

Cited by 576 publications

(413 citation statements)

References 29 publications

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“…Serum ALT levels are usually continuously or intermittently elevated, but the height of elevations correlates poorly with disease activity and at least one third of infected persons have persistently normal ALT levels. 45 In patients with persistently normal serum ALT levels, the underlying disease is usually, but not always, mild and nonprogre~sive.~5-~9…”

Section: Serological Course Of Chronic Hepatitis Cmentioning

confidence: 99%

Course and outcome of hepatitis C

2002

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The hepatitis C virus (HCV) is a small enveloped RNA virus belonging to the family flaviviridae and genus hepacivirus. The HCV RNA genome is 9,600 nucleotides in length and encodes a single polyprotein that is post-translationally cleaved into 10 polypeptides including t3 structural (C, El, and E2) and multiple nonstructural proteins ( [NS] NS2 to NS5). The NS proteins include enzymes necessary for protein processing (proteases) and viral replication (RNA polymerase). The virus replicates at a high rate in the liver and has marked sequence heterogeneity. There are 6 genotypes and more than 90 subtypes of HCV, the most common in the United States being l a and l b (approximately 75%), 2a and 2b (approximately 15%0), and 3 (approximately 7%). Acute hepatitis C is marked by appearance of HCV RNA in serum within 1 to 2 weeks of exposure followed by serum alanine aminotransferase (ALT) elevations, and then symptoms and jaundice. Antibody to HCV (anti-HCV) tends to arise late. In acute resolving hepatitis, HCV RNA is cleared and serum ALT levels fall to normal. However, 55% to 85% of patients do not clear virus, but develop chronic hepatitis C. Chronic hepatitis C is often asymptomatic, but is usually associated with persistent or fluctuating elevations in ALT levels. The chronic sequelae of hepatitis C include progressive hepatic fibrosis, cirrhosis, and hepatocellular carcinoma. Extra-hepatic manifestations include sicca syndrome, cryoglobulinemia, glomerulonephritis, and porphyria cutanea tarda. Knowledge of the course and outcome of hepatitis C is important in developing approaches to management and therapy. (HEPATOLOGY 2002;36:S21-S29.) H epatitis C is caused by a small RNA virus that belongs to the family flaviviridae and is the sole member of the genus hepacivirus.1.2 First identified in 1989,"* the hepatitis C virus (HCV) has a singlestranded RNA genome that is approximately 9.6 kilobases in length and encodes a single, large polyprotein of about 3,000 amino acids.5 The HCV-encoded polyprotein is cleaved post-translationally into multiple structural and nonstructural (NS) peptides: structural components consisting of a nucleocapsid core (C) and 2 envelope glycoproteins (El and E2) and the NS proteins being labeled NS2 through NS5 (Fig. l ) dependent RNA polymerase activity essential for RNA viral replication. These enzymatic activities are potential targets for antiviral compounds. The HCV genome also has important and highly conserved 5' and 3' untranslated regions.5-7 The 5' untranslated region has an internal ribosomal entry site essential for initiation of viral protein translation, and the 3' untranslated region has structured RNA elements essential for both viral replication and translation (Fig. 1).There are no robust cell culture systems for propagation of HCV, nor are there simple small animal models of the infection, so that the replicative cycle of the virus has largely been deduced from that of other flaviviruses. Hepatitis C virus replicates in the cytoplasm of hepatocytes where it is not direct...

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Section: Serological Course Of Chronic Hepatitis Cmentioning

confidence: 99%

Course and outcome of hepatitis C

2002

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“…Applying these exclusion criteria eliminated some reports which are often cited as evidence of HCV prevalence in NIDUs (Conry-Cantilena et al, 1996;Fingerhood et al, 1993;Shirin et al, 2000;Wada et al, 1999). Additionally, we excluded reports that provided only aggregate estimates combining IDUs and never-injectors.…”

Section: Exclusion Criteriamentioning

confidence: 99%

Non-injection drug use and Hepatitis C Virus: A systematic review

Scheinmann

Hagan

Leluţiu-Weinberger

et al. 2007

Drug and Alcohol Dependence

168

121

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This systematic review examined the evidence on the prevalence of the Hepatitis C virus (HCV) in non-injecting drug users (NIDUs) who sniff, smoke or snort drugs such as heroin, cocaine, crack or methamphetamine. The search included studies published from January 1989 to January 2006. Twenty-eight eligible studies were identified and the prevalence of HCV in these NIDU populations ranged from 2.3% to 35.3%. There was substantial variation in study focus and in the quality of the NIDU data presented in the studies. The results of our systematic review suggested that there are important gaps in the research of HCV in NIDUs. We identified a problem of study focus; much of the research did not aim to study HCV in users of non-injection drugs. Instead, NIDUs were typically included as a secondary research concern, with a principal focus on the problem of transmission of HCV in IDU populations. Despite methodological issues, HCV prevalence in this population is much higher than in a non-drug using population, even though some IDUs might have inadvertently been included in the NIDU samples. These studies point to a real problem of HCV in NIDU populations, but the causal pathway to infection remains unclear.

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“…Only a fraction of acutely infected individuals are able to clear the infection spontaneously, whereas about 80% of the infected individuals develop a chronic infection. 1,2 The symptoms are initially mild in these persistently infected patients, and it may take decades before the serious consequences of chronic HCV infection become apparent. Patients with chronic HCV are at increased risk for developing liver fibrosis, cirrhosis, and/or hepatocellular carcinoma.…”

Section: Hepatitis C Virus Pathology and Biologymentioning

confidence: 99%

Experimental models for hepatitis C viral infection

Boonstra¹,

Laan²,

Vanwolleghem³

et al. 2009

Hepatology

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Hepatitis C virus (HCV) infection is a leading cause of chronic liver disease. The majority of infected individuals develop a persistent infection, which is associated with a high risk of liver cirrhosis and hepatocellular carcinoma. Since its discovery 20 years ago, progress in our understanding of this virus has been suboptimal due to the lack of good model systems. However, in the past decade this has greatly accelerated with the development of various in vitro cell culture systems and in vivo small-animal models. These systems have made a major impact on the field of HCV research, and have provided important breakthroughs in our understanding of HCV infection and replication. Importantly, the in vitro cell culture systems and the small-animal models have allowed preclinical testing of numerous novel antiviral compounds for the treatment of chronic HCV infection. In this article, we give an overview of current models, discuss their limitations, and provide future perspectives for research directed at the prevention and cure of hepatitis C. (HEPATOLOGY 2009;50:1646-1655.) Hepatitis C Virus Pathology and BiologyThe hepatitis C virus (HCV) is considered a successful pathogen in establishing persistent infections by evading the immune system. Only a fraction of acutely infected individuals are able to clear the infection spontaneously, whereas about 80% of the infected individuals develop a chronic infection. 1,2 The symptoms are initially mild in these persistently infected patients, and it may take decades before the serious consequences of chronic HCV infection become apparent. Patients with chronic HCV are at increased risk for developing liver fibrosis, cirrhosis, and/or hepatocellular carcinoma. Currently, these longterm complications of chronic HCV infection are the leading indication for liver transplantation. 3,4 Because of the high incidence of new infections by blood transfusions in the 1980s before discovery of the virus, and because morbidity associated with chronic HCV infections generally takes decades to develop, it is expected that the burden of disease in the near future will rise dramatically.HCV is an enveloped flavivirus, with a positivestranded RNA genome of approximately 9600 nucleotides and is composed of a single open reading frame, which encodes a polyprotein precursor of approximately 3000 amino acids. The coding region is flanked by 5Ј and 3Ј noncoding regions, which are important for the regulation of genomic duplication as well as initiation of translation. The single polyprotein is cleaved by host and viral proteases into individual structural and nonstructural (NS) proteins (Fig. 1A). Replication of the HCV genome involves the synthesis of a full-length negative-stranded RNA intermediate, which in turn provides a template for the de novo production of positive-stranded RNA. Both these synthesis steps are mediated by the viral RNA-dependent RNA polymerase NS5B. 5-7 NS5B lacks proofreading abilities, and this leads to a high mutation rate and the generation of numerous quasispecies. ...

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Routes of Infection, Viremia, and Liver Disease in Blood Donors Found to Have Hepatitis C Virus Infection

Cited by 576 publications

References 29 publications

Course and outcome of hepatitis C

Course and outcome of hepatitis C

Non-injection drug use and Hepatitis C Virus: A systematic review

Experimental models for hepatitis C viral infection

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