non-B Hepatitis Virus Research Articles

Hepatitis C in 2020: A North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Position Paper.

In 1989, a collaboration between the Centers for Disease Control (CDC) and a California biotechnology company identified the hepatitis C virus (HCV, formerly known as non-A, non-B hepatitis virus) as the causative agent in the epidemic of silent posttransfusion hepatitis resulting in cirrhosis. We now know that, the HCV genome is a 9.6 kb positive, single-stranded RNA. A single open reading frame encodes a 3011 amino acid residue polyprotein that undergoes proteolysis to yield 10 individual gene products, consisting of 3 structural proteins (core and envelope glycoproteins E1 and E2) and 7 nonstructural (NS) proteins (p7, NS2, NS3, NS4A, NS4B, NS5A, and NS5B), which participate in posttranslational proteolytic processing and replication of HCV genetic material. Less than 25 years later, a new class of medications, known as direct-acting antivirals (DAAs) which target these proteins, were introduced to treat HCV infection. These highly effective antiviral agents are now approved for use in children as young as 3 years of age and have demonstrated sustained virologic responses exceeding 90% in most genotypes. Although tremendous scientific progress has been made, the incidence of acute HCV infections has increased by 4-fold since 2005, compounded in the last decade by a surge in opioid and intravenous drug use. Unfortunately, awareness of this deadly hepatotropic virus among members of the lay public remains limited. Patient education, advocacy, and counseling must, therefore, complement the availability of curative treatments against HCV infection if this virus is to be eradicated.

HEPATITIS C

Background: Hepatitis C virus (HCV) is the most communal source of non-A,non-B viral hepatitis in the world. The disease is illusory, and the majority of patients do notacquire jaundice at its onset. Treatment of hepatitis C with interferon attained a sustainedvirological response (SVR) in almost 50% of the patients with HCV infection. Viral genotype isimportant to determine the response. The present study aims to provide the incidence of relapseof HCV in patients taking interferon therapy and to identify the predictors for relapse. StudyDesign: Retrospective observational study. Setting: Department of Medicine, DHQ TeachingHospital, Sargodha. Period: Two years. Methods: A total of 60 patients were retrospectivelyevaluated for this study. The exclusion criteria include the patients co- infected with hepatitisB virus or HIV. All the patients were monitored 2, 4, 8, 12, 16, and 24 weeks after the endof treatment with interferon alpha. Results: We observed that the patients with relapse weresignificantly older and heavier (P value < 0.05). At the start of treatment, viral load was higherin relapsed patients (P value < 0.04). Conclusion: On the bases of our study findings, we canconclude that low incidence of relapse occurred with interferon therapy. High ALT level, viralloads, older age and obesity were some of strong predictors of relapse among HCV patients.

Unexplained diarrhoea in HIV-1 infected individuals.

BackgroundGastrointestinal symptoms, in particular diarrhoea, are common in non-treated HIV-1 infected individuals. Although various enteric pathogens have been implicated, the aetiology of diarrhoea remains unexplained in a large proportion of HIV-1 infected patients. Our aim is to identify the cause of diarrhoea for patients that remain negative in routine diagnostics.MethodsIn this study stool samples of 196 HIV-1 infected persons, including 29 persons with diarrhoea, were examined for enteropathogens and HIV-1. A search for unknown and unexpected viruses was performed using virus discovery cDNA-AFLP combined with Roche-454 sequencing (VIDISCA-454).ResultsHIV-1 RNA was detected in stool of 19 patients with diarrhoea (66%) compared to 75 patients (45%) without diarrhoea. In 19 of the 29 diarrhoea cases a known enteropathogen could be identified (66%). Next to these known causative agents, a range of recently identified viruses was identified via VIDISCA-454: cosavirus, Aichi virus, human gyrovirus, and non-A non-B hepatitis virus. Moreover, a novel virus was detected which was named immunodeficiency-associated stool virus (IASvirus). However, PCR based screening for these viruses showed that none of these novel viruses was associated with diarrhoea. Notably, among the 34% enteropathogen-negative cases, HIV-1 RNA shedding in stool was more frequently observed (80%) compared to enteropathogen-positive cases (47%), indicating that HIV-1 itself is the most likely candidate to be involved in diarrhoea.ConclusionUnexplained diarrhoea in HIV-1 infected patients is probably not caused by recently described or previously unknown pathogens, but it is more likely that HIV-1 itself plays a role in intestinal mucosal abnormalities which leads to diarrhoea.

Molecular virology in transfusion medicine laboratory.

and antibody to HBV core antigen (anti-HBc) testing began in the 80s to reduce transmission of non-A, non-B viral hepatitis. Then, the advent of the human immunodeficiency virus (HIV) epidemic and the rapidly following identification of hepatitis C virus (HCV) triggered unprecedented efforts to avoid the transmission of these new blood-borne viruses, and the implementation of antibody assays for both of these agents. To exclude individuals at risk for transmissible viral infection, donor screening process has been developed and implemented that includes the medical history of the candidate donor, a brief physical examination, and serologic testing. The next critical step in reducing viral TTI was achieved with the implementation of NAT technology 2 . Rapid progress and constant improvements in nucleic acid amplification technologies resulted in an unprecedented technological turning point in the molecular diagnostic and characterisation of viral infections. NAT combines the advantages of direct and highly sequence-specific detection of viral genomes (DNA or RNA) with an analytic sensitivity that is several orders of magnitude greater than that of antigen detection or virus isolation methods. Adequate specificity and high sensitivity combined with high throughput and the increasing availability of commercial assays, made NAT particularly suitable to screen blood donations for the presence of viral genomes. However, the considerable cost of NAT and challenges in automation led the users to develop strategies based on pooling of multiple donor samples

A Comparative Analysis of Hepatocellular Carcinoma after Hepatic Resection in Young versus Elderly Patients

PurposeThe aim of this study was to investigate the clinical outcomes after surgical treatment of hepatocellular carcinoma (HCC) in the elderly patients compared with younger patients. MethodsClinicopathological data and treatment outcomes in 61 elderly (≥70 years old) and 90 younger (≤40 years old) patients with HCC who underwent curative liver resection between 2000 and 2010 were retrospectively collected and compared using various parameters. ResultsThe older HCC group was more likely to have hepatitis C virus and non-B non-C hepatitis virus infection, higher values of indocyanine green retention at 15 min (ICGR)15, more preoperative comorbidities, and more postoperative complications. There were no significant differences in intraoperative parameters and pathologic features. The recurrence rate, overall survival and disease-free survival rates were similar amongst the two groups. The only independent prognostic factor of overall survival was postoperative complications. ConclusionOur findings suggest that age by itself does not have an adverse effect on operative outcomes, including long-term prognosis. For young and elderly HCC patients, hepatic resection is a safe and effective treatment.

Clinicopathologic characteristics of patients with non-B non-C hepatitis virus hepatocellular carcinoma after hepatectomy

BackgroundA substantial population of hepatocellular carcinoma (HCC) patients is negative for markers of hepatitis B virus and hepatitis C virus (HCV) infection (non-B non-C hepatitis virus [NBC]). MethodsClinicopathologic data and outcomes were compared retrospectively for HCC patients with hepatitis B virus, HCV, and NBC who had undergone hepatectomy. ResultsThe TNM stage was significantly higher, and the prevalence of cirrhosis was significantly lower, in the NBC group compared with the HCV group. Among patients with a maximum tumor diameter of 5 cm or less, the survival rates were significantly higher in the NBC group than in the HCV group. Multivariate analysis revealed that preoperative serum des-gamma-carboxy prothrombin (DCP) level was a prognostic factor for survival in NBC–HCC patients. The DCP/tumor size ratio was significantly higher in NBC–HCC patients with normal liver histology than in patients with hepatitis or cirrhosis. ConclusionsNBC–HCC patients had more advanced tumors compared with HCV–HCC patients, but significantly higher survival rates. Measurement of DCP potentially is significant for early diagnosis of NBC HCC, which may increase the chance of curative therapy without recurrence.

Focus

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Hepatitis C virus infection and lymphoma

Apart from its well known role as an etiological agent for non-A and non-B viral hepatitis, there is growing evidence that hepatitis C virus is associated to B-cell non-Hodgkin lymphoma. The association between HCV and lymphoproliferative disorders has been recently postulated based on epidemiological data, biological studies and clinical observations. Although various subtypes of lymphomas appear to be associated to HCV, diffuse large B-cell lymphoma, small lymphocytic lymphoma/chronic lymphocytic leukemia and marginal zone lymphoma appeared to be particularly represented among HCV-positive patients. The causative role of HCV in those disorders has been further supported by the response to antiviral therapy. Despite a better understanding of pathophysiological processes at stake leading from HCV infection to overt lymphoma, many issues still need to be further elucidated. Although HCV has been demonstrated to directly infect peripheral blood mononuclear cells both in vitro and, in some cases, in vivo, a strong body of evidence rather supports the hypothesis of an indirect transformation mechanism by which sustained antigenic stimulation leads from oligoclonal to monoclonal expansion and sometimes to lymphoma, probably through secondary oncogenic events. Here, we review epidemiological and biological studies, as well as clinical data on antiviral therapy, linking HCV-infection to B-cell non-Hodgkin lymphoma.

Discovery of the hepatitis C virus

After nearly 6 years of intensive investigations between 1982 and 1988 in my laboratory at Chiron corporation, in which numerous molecular biological methods were used to investigate the viral aetiology of parenterally transmitted non-A, non-B viral hepatitis (NANBH), a single cDNA clone (5-1-1) was isolated that was shown to be derived from a new flavi-like virus, termed the hepatitis C virus (HCV). After screening hundreds of millions of bacterial cDNA clones derived from different liver and plasma samples obtained from experimentally infected chimpanzees, a single HCV clone was eventually isolated using a novel, blind immunoscreening method in which antibodies derived from a clinically diagnosed NANBH patient were used to identify a cDNA clone encoding an immunodominant epitope within HCV nonstructural protein 4. Its viral origin was demonstrated by its specific hybridization to a large single-stranded RNA molecule of approximately 10,000 nucleotides found only in NANBH-infected samples that shared distant sequence identity with flaviviruses. Further, HCV clone 5-1-1 was shown to be extrachromosomal and to encode an antigen eliciting antibody seroconversion only in NANBH-infected chimpanzees and humans. Subsequent work demonstrated that HCV was the principal cause of parenterally transmitted NANBH around the world, with an estimated 170 million global carriers and that blood screening tests detecting circulating HCV antibodies and viral RNA could effectively eradicate the transmission of transfusion-associated NANBH. Key viral-encoded enzymes essential to its life cycle are now the targets of vigorous, ongoing drug development activities, and the feasibility of successful vaccination strategies has been demonstrated using the valuable chimpanzee model, without which any progress on HCV would not have been possible. My colleagues and coworkers who made essential contributions to the discovery of HCV were George Kuo, who had his own laboratory at Chiron and who provided intellectual and practical input, Dan Bradley of the Centers for Disease Control and Prevention, who provided a large supply of well-characterized chimpanzee samples and knowledge of the NANBH field, and Qui-Lim Choo, in my own laboratory, who provided many years of outstandingly dedicated and precise molecular biology expertise.

Hepatitis E virus as an etiology of acute exacerbation of previously unrecognized asymptomatic patients with hepatitis B virus‐related chronic liver disease

Hepatitis E virus (HEV) has recently been implicated in episodes of acute decompensation in patients having underlying chronic liver disease (CLD) of varying etiology. However, HEV as a cause of acute exacerbation of previously asymptomatic and unrecognized hepatitis B virus (HBV)-infected patients is less well described. The aim of the present study was to investigate the etiology of acute exacerbation of previously asymptomatic and unrecognized HBV-infected patients and to evaluate the relative role of HEV. We also investigated the effect of superinfection on the clinical spectrum of underlying HBV infection. Forty-three patients presented with the following were retrospectively analyzed: (i) clinical features suggestive of acute hepatitis; (ii) with hepatitis B surface antigen (HBsAg) (+); (iii) IgM hepatitis B core antibody (IgM anti-HBc) (-); (iv) no previous history of liver disease; (v) no features suggestive of CLD at presentation; (vi) HBsAg remaining (+) for at least 12 months on follow up; and (vii) having a follow-up biopsy during the convalescent phase showing evidence of chronic hepatitis B. Of the 43 patients, 21 were hepatitis e antigen (HBeAg) (+) (Gr.1) and 22 HBeAg (-) (Gr.2) at presentation. In Gr.1, only two (9.5%) had superinfection (both with hepatitis A virus), whereas in Gr.2, 11 (50%) had superinfection (27.3% hepatitis E, 13.6% hepatitis A and 9.1% both) (P = 0.007). In Gr.1, the remaining 19 (90.5%) patients had spontaneous exacerbation (immune clearance with spontaneous seroconversion) whereas in Gr.2, the remaining 11 (50%) had spontaneous exacerbation (due to reactivation). Overall, HEV superinfection contributed to 20% of acute exacerbation episodes and, in particular, 36% of episodes in initially HBeAg (-) patients. Time to alanine aminotransferase normalization was longer in patients with superinfection (n = 13) as compared to spontaneous exacerbation (n = 30) (median [range] 36 [8-48]vs 16 [6-36] weeks, P = 0.001). During convalescence, there was no significant difference between histological activity index score (median [range] 8 [4-11]vs 8 [4-16] weeks, P = 0.629) and fibrosis scores (median [range] 3.5 [1-4]vs 2 [1-4] weeks, P = 0.099] on liver biopsy after recovery among patients with acute exacerbation due to superinfection and spontaneous exacerbation. Acute exacerbations in HBeAg (+) patients are most often due to spontaneous viral activation, while in HBeAg (-) patients, superinfection with non-B hepatitis viruses and spontaneous viral activation are equally common. HEV is an important cause of acute exacerbation in previously asymptomatic and unrecognized patients with HBV-related CLD.

Hepatitis C virus and lymphoma

Hepatitis C virus (HCV) is well known for its aetiological role in chronic non-A, non-B viral hepatitis, liver cirrhosis and hepatocellular carcinoma; in addition, the virus has also been implicated...

DETERMINATION OF HEPATITIS C VIRUS GENOTYPES BY MELTING-CURVE ANALYSIS OF QUANTITATIVE POLYMERASE CHAIN REACTION PRODUCTS

Hepatitis C virus (HCV) is the major causative agent of non-A and non-B viral hepatitis. Factors associated with disease progression following HCV infection include the viral genotype, the patient’s alcohol consumption, and viral load. In this study, the COBAS AMPLICOR HCV MONITOR test, a commercially available quantitative assay for HCV RNA, was used for HCV genotyping analysis. Amplification products obtained from 100 HCV-positive cases were subjected to real-time polymerase chain reaction (PCR) typing using a single pair of fluorescence resonance energy transfer (FRET) probes and melting-curve analysis. Of 100 samples tested, two inhibited the PCR, two samples yielded discrepancies between our results and the reference laboratory results, and the remaining samples provided correct typing. The present report suggests that HCV genotypes can be determined rapidly with FRET probes directly from COBAS AMPLICOR MONITOR test PCR products.

Changing Patterns of Acute Viral Hepatitis at a Major Urban Referral Center in Egypt

Changes in the viral etiology of hospitalized patients can inform us of changes in the overall epidemiology of acute viral hepatitis infections. We hypothesized that improvements in health care and sanitation in the past 2 decades in Egypt have significantly impacted the viral causes of acute viral hepatitis in hospitalized patients. We compared the viral causes of acute viral hepatitis at a major urban referral center with results reported from the same center 20 years earlier. Over a period of 10 months, 200 consecutive inpatients with clinical acute viral hepatitis were enrolled in the study, and serum samples were tested for hepatitis A through E, cytomegalovirus, and Epstein-Barr virus. The frequency of acute hepatitis B virus infection as a cause of symptomatic hepatitis decreased from 43.4% in 1983 to 28.5% in 2002 (P<.01), and acute hepatitis A virus infection increased from 2.1% in 1983 to 34% in 2002 (P<.01), and occurred at older ages. In 1983, non-A, non-B hepatitis virus infection caused acute viral hepatitis in 38.7% of cases, compared with 31% in the present study (P=.12). The mean alanine aminotransferase level was highest in patients with combined infections, and clinical presentation did not distinguish between different viral etiologies of hepatitis. A significant decrease in hepatitis B virus infection and an increase in hepatitis A virus infection have occurred since the earlier study was performed in 1983. The decrease in hepatitis B virus infection is attributable to the steep decrease in hepatitis B virus infection among children that resulted from the universal hepatitis B virus immunization of infants that was initiated in 1991. The increase in clinical hepatitis A virus infection occurred in older patients and could be attributed to improved sanitation that delayed individuals' initial exposures to the virus.

Determination of hepatitis C virus genotypes by melting-curve analysis of quantitative polymerase chain reaction products

Hepatitis C virus (HCV) is the major causative agent of non-A and non-B viral hepatitis. Factors associated with disease progression following HCV infection include the viral genotype, the patient's alcohol consumption and viral load. In this study, the COBAS AMPLICOR HCV MONITOR test, a commercially available quantitative assay for HCV RNA, was used for HCV genotyping analysis. Amplification products obtained from 100 HCV-positive cases were subjected to real-time polymerase chain reaction (PCR) typing using a single pair of fluorescence resonance energy transfer (FRET) probes and melting-curve analysis. Of 100 samples tested, two inhibited the PCR, two samples yielded discrepancies between our results and the reference laboratory results and the remaining samples provided correct typing. The present report suggests that HCV genotypes can be determined rapidly with FRET probes directly from COBAS AMPLICOR MONITOR test PCR products.

Impact of Surveillance on Survival of Patients With Initial Hepatocellular Carcinoma: A Study From Japan

We investigated trends in the prediagnostic surveillance of patients in whom hepatocellular carcinoma (HCC) was diagnosed, and evaluated the impact of these trends on early detection of HCC and on patient survival. We evaluated 1641 patients in whom HCC initially was diagnosed during the period of 1968 to 2004. Patients were grouped by the year of diagnosis: 1968-1980 (n = 151), 1981-1990 (n = 409), 1991-2000 (n = 754), and 2001-2004 (n = 324). They also were classified according to whether they were in surveillance and its context before the diagnosis of HCC: patients undergoing follow-up evaluation in our center (group A), those followed up and referred by a primary care physician (group B), and those not in surveillance (group C). The percentage of patients in groups A and B increased markedly over time. Early stage HCC was significantly more prevalent in groups A and B than in group C, and the frequency of early stage HCC increased sequentially. The patient survival rate was highest in group A, followed by that in groups B and C in that order; patient survival improved sequentially. The percentage of patients undergoing in-center surveillance or referred by a primary care physician increased, resulting in increased early detection of HCC and improved patient survival.

Parvovirus B19 and Aplastic Anemia: Case Control Study: Preliminary Report from the ITESM Hematology Study Group.

Aplastic anemia (AA) is a classic bone marrow failure syndrome simply defined as peripheral blood pancytopenia and a hypocelular bone marrow, yet the diagnosis must be made by excluding other causes of bone marrow failure. The incidence rate of AA reported by the International Aplastic Anemia and Agranulocytosis Study (IAAAS) in the 1980s was 2 cases per 1 million people. This disease is known to be caused by exposure to radiation, chemotherapy and some viral agents, yet most of the cases are idiopathic. Epstein Barr virus and non-A, non-B or non-C Hepatitis virus have classically been related to the development of some AA cases. Recently there have been some reports of AA following Parvovirus B19 (PvB19) infection. This virus, the only parvoviridae virus capable of infecting humans, attacks erythrocyte precursors attaching to the P antigen in their surface and requiring Beta1 integrin for viral entry. Although PvB19 seems to infect only erytroid precursors, it is widely recognized that the infection with this virus can cause not only anemia, but neutropenia and thrombocytopenia as well, producing aplastic crisis of varying intensity. A correlation has recently been found between PvB19 DNA in peripheral blood and AA in children. We pretend to corroborate this observation and include adult patients in order to improve our understanding of the relationship between PvB19 and AA. So far we have taken peripheral blood samples from 9 AA patients and 9 controls paired by age, sex and community; we plan to include 100 AA patients and their controls from several hospitals around Mexico. DNA was extracted using the PUREGENE DNA extraction kit (Gentra, Minneapolis MN). Nested PCR was performed using the sense primer (P1) 5-AATACACTGTGGTTTTATGGGCCG-3, antisense (P2) 5-CCATTGCTGGTTATAACCACAGGT-3 for the first round and the sense primer (P3) 5-AATGAAAACTTTCCATTTAATGATGTAG-3 and antisense primer (P4) 5-CTAAAATGGCTTTTGCAGCTTCTAC-3for the second round. A DNA sample from a patient with active infectious mononucleosis with positive IgG and IgM against PvB19 in serum was used as positive control. Two samples from the AA group (22%) and 1 from the control group (11%) have turned positive for PvB19 DNA. The reported incidence for the presence of this virusDNA in the peripheral blood of the population is 3%. We expect that, as the number of patients grows, the percentage of positive samples in the control group will decrease, while the percentage of positive samples in the AA group will rise or be sustained. Our partial results point towards a possible relationship between AA and the presence of PvB19 DNA in the peripheral blood cells. It is possible that this virus is one of many factors capable of precipitating the development of AA by limiting the bone marrows capacity to produce blood cells. We are in the process of gathering more samples to prove if a relationship really exists and, if so, future studies will likely shed light upon the mechanism by which PvB19 contributes to the development of AA and other marrow failure syndromes.

The burden of hepatitis C in the United States.

According to the third National Health and Nutrition Examination Survey (NHANES), 3.9 million of the U.S. civilian population have been infected with hepatitis C virus (HCV), of whom 2.7 million (74%) have chronic infection. Hepatitis C virus infection is most common among non-Caucasian men, ages 30 to 49 years. Moreover, the prevalence of antibody to hepatitis C virus in groups not represented in the NHANES sample, such as the homeless or incarcerated, may be as high as 40%. The age-adjusted death rate for non-A, non-B viral hepatitis increased from 0.4 to 1.8 deaths per 100,000 persons per year between 1982 and 1999. In 1999, the first year hepatitis C was reported separately, there were 3,759 deaths attributed to HCV, although this is likely an underestimate. There was a 5-fold increase in the annual number of patients with HCV who underwent liver transplantation between 1990 and 2000. Currently, more than one third of liver transplant candidates have HCV. Inpatient care of HCV-related liver disease has also been increasing. In 1998, an estimated 140,000 discharges listed an HCV-related diagnosis, accounting for 2% of discharges from non-federal acute care hospitals in the United States. The total direct health care cost associated with HCV is estimated to have exceeded $1 billion in 1998. Future projections predict a 4-fold increase between 1990 and 2015 in persons at risk of chronic liver disease (i.e., those with infection for 20 years or longer), suggesting a continued rise in the burden of HCV in the United States in the foreseeable future.

The burden of hepatitis C in the United States

According to the third National Health and Nutrition Examination Survey (NHANES), 3.9 million of the U.S. civilian population have been infected with hepatitis C virus (HCV), of whom 2.7 million (74%) have chronic infection. Hepatitis C virus infection is most common among non-Caucasian men, ages 30 to 49 years. Moreover, the prevalence of antibody to hepatitis C virus in groups not represented in the NHANES sample, such as the homeless or incarcerated, may be as high as 40%. The age-adjusted death rate for non-A, non-B viral hepatitis increased from 0.4 to 1.8 deaths per 100,000 persons per year between 1982 and 1999. In 1999, the first year hepatitis C was reported separately, there were 3,759 deaths attributed to HCV, although this is likely an underestimate. There was a 5-fold increase in the annual number of patients with HCV who underwent liver transplantation between 1990 and 2000. Currently, more than one third of liver transplant candidates have HCV. Inpatient care of HCV-related liver disease has also been increasing. In 1998, an estimated 140,000 discharges listed an HCV-related diagnosis, accounting for 2% of discharges from non-federal acute care hospitals in the United States. The total direct health care cost associated with HCV is estimated to have exceeded $1 billion in 1998. Future projections predict a 4-fold increase between 1990 and 2015 in persons at risk of chronic liver disease (i.e., those with infection for 20 years or longer), suggesting a continued rise in the burden of HCV in the United States in the foreseeable future. (Hepatology 2002;36:S30-S34).

Choo QL, Kuo G, Weiner AJ, Overby LR, Bradley DW, Houghton M. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome [Science 1989;244:359–362

Abstract: A random-primed complementary DNA library was constructed from plasme containing the uncharacterized non-A, non-B hepatitis (NANBH) agent and screend with serum from a patient diagnosed with NANBH. A complementary DNA clone was isolated that was shown to encode an antigen associated specifically with NANBH infections. This clone is not derived from host DNA but from an RNA molecule present in NANBH infections that consists of at least 10,000 nucleotides and this is positive-stranded with respect to the encoded NANBH antigen. These data indicate that this clone is derived from the genome of the NANBH agent and are consistent with the agent being similar to the togaviridae or flaviviridae. This molecular approach should be of great value in the isolation and characterization of other unidentified infectious agents.

Advances in the Molecular Diagnosis of Hepatitis C and Their Clinical Implications

Advances in the Molecular Diagnosis of Hepatitis C and Their Clinical Implications