Hepatitis C virus infects an estimated 170 million people worldwide. It is a major cause of liver cirrhosis, end-stage liver disease and hepatocellular carcinoma. It is also a leading cause of liver transplant in the USA. The virus is primarily transmitted parenterally, but there is significant mother-to-child transmission. Partly due to the virus's genetic diversity, it evades the host immune response and it has been difficult to identify candidate vaccines. However, significant advances have been made in the treatment of chronic hepatitis C virus infection. Currently, the combination of pegylated interferon-alpha and ribavirin is the standard treatment for chronic hepatitis C virus infection, and leads to long-term eradication of the virus in approximately 54% of people. Treatment response is dependent on the infecting genotype, with 76 to 80% of those with genotypes 2 and 3, but only approximately 40% with genotype 1 or 4 achieving a sustained virologic response. Since treatment is expensive and associated with significant adverse effects, more effective strategies for the prevention of transmission are needed, especially in resource-limited countries, where the burden of disease is the highest.
"More than 170 million people (3% of the world population) are infected with hepatitis C virus (HCV) . Chronic HCV infection is a major cause of liver cirrhosis and hepatocellular carcinoma (HCC), as well as liver failure. "
[Show abstract][Hide abstract] ABSTRACT: Direct-acting antiviral (DAAs) agents for hepatitis C virus (HCV) span a variety of targets, including proteins encoded by the NS3/4A, NS4B, NS5A, and NS5B genes. Treatment with DAAs has been shown to select variants with sequence changes in the HCV genome encoding amino acids that may confer resistance to the treatment. In order to assess these effects in patients, a Reverse Transcription Polymerase Chain Reaction (RT-PCR) method was developed to sequence these regions of HCV from patient plasma.
A method was developed to amplify and sequence genotype 1 HCV RNA from patient plasma. Optimization of HCV RNA isolation, cDNA synthesis, and nested PCR steps were performed. The optimization of HCV RNA isolation, design of RT-PCR primers, optimization of RT-PCR amplification conditions and reagents, and the evaluation of the RT-PCR method performance is described.
The optimized method is able to successfully, accurately, and reproducibly amplify near full-length genotype 1 HCV RNA containing a wide range of concentrations (103 to 108 IU/mL) with a success rate of 97%. The lower limit of detection was determined to be 1000 IU/mL HCV RNA.
This assay allows viral sequencing of all regions targeted by the most common DAAs currently in development, as well as the possibility to determine linkage between variants conferring resistance to multiple DAAs used in combination therapy.
"Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are two of the most common chronic viral liver diseases (1-3). Hepatocellular carcinoma (HCC) and liver cirrhosis, as chronic sequelaes of viral hepatitis, lead to approximately one million deaths per year (1), while HCV is the number one cause of liver transplantation in the United States and many other countries (4). Moreover, even though HBV vaccination in the majority of countries, including Iran, is expected to decrease the prevalence of this infection, it will take decades to determine the efficiency of these vaccination programs (5). "
[Show abstract][Hide abstract] ABSTRACT: There have been studies regarding the prevalence of hepatitis B surface antigen (HBsAg) and anti-hepatitis C antibody (HCVAb) in Iran. However, the majority of these have reported a variety of rates, depending on their study population, which limits the generalizability of their results to the general population. On the other hand, cultural diversity in the different provinces of Iran also necessitates the performing separate population-based studies in the various regions.
To evaluate the population-based prevalence of HBsAg and HCVAb and their correlates in Zahedan City, Iran.
Included in this study were 2587 individuals, using a random and cluster sampling approach. The participants were drawn from the Family Registry of the public health centers in Zahedan City, Iran, from 2008 to 2009. Following data collection from the interviews, subjects were assessed for seropositivity of HBsAg and HCVAb. We then calculated the prevalence of HBsAg and HCVAb, and evaluated these viral markers for an association with; age, sex and potential risk factors.
Weighted seroprevalence of HBsAg and HCVAb was 2.5% (CI 95% : 1.9 to 3.3 %) and 0.5% (CI 95% : 0.27 to 0.9 %), respectively. Prevalence of HBsAg increased significantly with age (P value < 0.001), but this was not true for HCVAb (P value: 0.67). We observed no sex dominance in the prevalence of HBsAg (3.2% and 2.2% for males and females, respectively, P value: 0.15) or HCVAb (0.4% and 0.7% for males and females, respectively, P value: 0.27). In a multivariate regression analysis, every additional year in age resulted in a 2% increment in the odds of HBsAg seropositivity. HBsAg was also three times more prevalent among married, than single subjects (with a P value reaching toward significance: 0.065) in multivariate analysis. Prevalence of HCVAb did not differ with respect to any of the potential risk factors.
This is the first population-based study on the prevalence of HCVAb and one of the few population based studies on HBsAg in Zahedan City. We detected lower prevalence rates of HBsAg and HCVAb than in previous studies conducted in Zahedan City. In addition to improvements in social awareness and general health elements, we think that the observed low prevalence rates have been achieved due to the efficiency of mass vaccination projects, implemented against HBV infection in Iran.
"We discern that chronic viral hepatitis is the prime candidate based on the above criteria. It is a massive problem worldwide [7-9] and Table 1 shows that it is the most common of the specific liver diseases in the UK population after alcohol damage. Moreover, chronic viral hepatitis can be reliably confirmed or excluded by means of a relatively inexpensive blood test [10,11]. "
[Show abstract][Hide abstract] ABSTRACT: Liver function tests (LFTs) are ordered in large numbers in primary care, and the Birmingham and Lambeth Liver Evaluation Testing Strategies (BALLETS) study was set up to assess their usefulness in patients with no pre-existing or self-evident liver disease. All patients were tested for chronic viral hepatitis thereby providing an opportunity to compare various strategies for detection of this serious treatable disease.
This study uses data from the BALLETS cohort to compare various testing strategies for viral hepatitis in patients who had received an abnormal LFT result. The aim was to inform a strategy for identification of patients with chronic viral hepatitis. We used a cost-minimisation analysis to define a base case and then calculated the incremental cost per case detected to inform a strategy that could guide testing for chronic viral hepatitis.
Of the 1,236 study patients with an abnormal LFT, 13 had chronic viral hepatitis (nine hepatitis B and four hepatitis C). The strategy advocated by the current guidelines (repeating the LFT with a view to testing for specific disease if it remained abnormal) was less efficient (more expensive per case detected) than a simple policy of testing all patients for viral hepatitis without repeating LFTs. A more selective strategy of viral testing all patients for viral hepatitis if they were born in countries where viral hepatitis was prevalent provided high efficiency with little loss of sensitivity. A notably high alanine aminotransferase (ALT) level (greater than twice the upper limit of normal) on the initial ALT test had high predictive value, but was insensitive, missing half the cases of viral infection.
Based on this analysis and on widely accepted clinical principles, a "fast and frugal" heuristic was produced to guide general practitioners with respect to diagnosing cases of viral hepatitis in asymptomatic patients with abnormal LFTs. It recommends testing all patients where a clear clinical indication of infection is present (e.g. evidence of intravenous drug use), followed by testing all patients who originated from countries where viral hepatitis is prevalent, and finally testing those who have a notably raised ALT level (more than twice the upper limit of normal). Patients not picked up by this efficient algorithm had a risk of chronic viral hepatitis that is lower than the general population.
BMC Family Practice 03/2011; 12(1):9. DOI:10.1186/1471-2296-12-9 · 1.67 Impact Factor
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