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Viral hepatitis is caused by several viruses known as hepatitis viruses. The most common types of hepatitis viruses include hepatitis A virus (HAV), B (HBC), C (HCV), D (HDV) and E (HEV). About 1.4 million people become infected by HAV around the world annually. More than 240 million people live with chronic HBV infection and about 600 thousand people die every year from acute or chronic HBV infection. About 150 million people globally have chronic HCV infection and more than 350 thousand people die every year due to HCV-related liver diseases (1). Hepatitis viruses are different in genomic type, antigenic patterns, mode of transmission, severity and chronicity, etc. (2). During recent years, some considerable efforts have been devoted toward development of various techniques to detect hepatitis virus derivative targets including: IgM and IgG for HAV, all serological markers (anti-HBc antibodies [IgM and IgG], anti-HBe antibody, HBeAg and HBsAg), and HBV DNA for HBV (3), anti-HCV antibodies and HCV RNA for HCV, anti-HDV antibodies and HDV antigen for HDV and anti-HEV antibodies and HEV RNA for HEV (4). Immunoassay methods were described as general and versatile techniques for identification of pathogenic agents (5). The most commonly and also traditionally used immunoassay techniques for detection of hepatitis viruses are RIA (6, 7) and ELISA (8). Immunochemiluminescent assay, and lateral flow immunoassay are among more advanced immunoassay techniques. Recently, molecular approaches have been converted into unavoidable implements to diagnose viral disease, with accurate and reliable results (9, 10). Widely utilized molecular methods for detection of hepatitis viruses relies on nucleic acid amplification. Signal, target and probe amplifications are described as formats of amplification based methods (11, 12). Nowadays the modern techniques for hepatitis detection are intellectual combinations between serological and molecular methods, jointed with nanotechnology, chemistry, electronics and high-tech apparatus. On the other hand, some newfound recognizer elements such as aptamers are emerging to help scientists to identify the hepatitis virus easier than past (13). In this review, it was intended to investigate the classical and modern techniques in diagnosis of hepatitis viruses and introduce the developed and advanced methods available in this field.
In this review article after determination of the main concepts and statement about the problem, attempts made to gather data about the aims and aspects, from major databases including PubMed, EMBASE and Scopus from 1970 to 2013. In this regard the most relevant keywords such as hepatitis viruses, classical and novel detection techniques, immunoassay, biosensors, molecular detection methods and many more were used to construct thesaurus in different databases. Irrespective to any classification, about 120 full articles and 50 abstracts were obtained from above mentioned databases. Thereafter different techniques and data were analyzed, categorized and compared with each other. Finally unpredictable, digressive and redundant data were discarded and the main collected points were arranged, summarized and divided into different sections.
Resultant items and findings about classical and modern approaches used for viral hepatitis diagnosis were collected in different parts including immunological methods, molecular approaches and advanced biosensors. An analytical outline of each class of detection method presented below.
Viral hepatitis is considered a dangerous public health problem worldwide. Diagnosis and treatment are the main goals to inhibit the spread of hepatitis viruses. Exact diagnosis of hepatitis virus types and infection stage for an effective treatment need a relatively broad knowledge about viral hepatitis infections. Each detection technique has its special advantages and limitations. EIAs are the most important serological assays used for hepatitis viruses’ detection. EIAs procedures are simple and convenient to set up and having nano-gram or sensitivity to low levels of target presence, few reagents requirement, quantitative and qualitative testing and capability of being automated are some of the advantages of EIAs. On the other hand they can be time-consuming and expensive devices. Rapid detection of viral hepatitis, soon after infection, is an urgent requirement to treat and prevent infection transmission. Development of molecular methods for diagnosis of viral genomic materials has revolutionized the detection procedure in clinical laboratories. Some of these techniques have been introduced as common laboratory tests but some others such as real-time PCR are applied as gold-standard and reference settings. The major advantages of molecular methods are having higher specificity and sensitivity and larger dynamic range of action compared to other diagnostic methods like serological assays. Regarding nucleic acid tests, requiring special instruments and post handling in some molecular tests and inability to indicate the pathogen viability are the main limitations. Biosensors have been described for label free detection of hepatitis viruses. Most of biosensors are based on the combination of existing molecular and immunological techniques coupled with optical, electrochemical, mass-sensitive and electrical sensing modules. The main advantages of these detection systems are offering a quantitative test for detection in cases with about 100 copies of hepatitis virus, in addition to automation, multiplexing analysis and throughput. It seems further studies are necessary to completely uniform the methods that can be established as universal recommendations for detection of hepatitis viruses.
