45-Year Follow-up of Hepatitis C Virus Infection in Healthy Young Adults

Seeff, Leonard B.; Miller, Richard N.; Rabkin, Charles S.; Buskell‐Bales, Zelma; Straley-Eason, Kelle D.; Smoak, Bonnie L.; Johnson, Leslye D.; Lee, Stephen R.; Kaplan, Edward L.

doi:10.7326/0003-4819-132-2-200001180-00003

Cited by 313 publications

(209 citation statements)

References 29 publications

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“…In our study, no patient developed cirrhosis after 15 years of infection. Similarly, Seeff et al [12] observed liver disease in only 11.8% of HCV-infected patients after 45 years of infection. In this study, analysis of the causes of mortality after this long period of time revealed that death was attributable to hepatitis C in only 5.9% of cases.…”

Section: Discussionmentioning

confidence: 99%

Effect of host-related factors on the intensity of liver fibrosis in patients with chronic hepatitis C virus infection

Costa¹,

Ferraz²,

Perez³

et al. 2002

Braz J Infect Dis

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There is increasing interest in the identification of factors associated with liver disease progression in patients infected with hepatitis C virus (HCV). We assessed host-related factors associated with a histologically advanced stage of this disease and determined the rate of liver fibrosis progression in HCV-infected patients. We included patients submitted to liver biopsy, who were anti-HCV and HCV RNA positive, who showed a parenteral risk factor (blood transfusion or intravenous drug use), and who gave information about alcohol consumption.Patients were divided into two groups for analysis: group 1 -grades 0 to 2; group 2 -grades 3 to 4. The groups were compared in terms of sex, age at the time of infection, estimated duration of infection and alcoholism Hepatitis C virus (HCV) infection affects people worldwide and about 170 million individuals are estimated to be chronically infected with HCV. Several aspects of the natural history of this disease are still not completely understood.After acute infection, viremia persists in 85% of the patients [1] and most of them develop chronic hepatitis. Different studies have shown variable rates of progression to cirrhosis in patients with chronic hepatitis C according to the group analyzed. Only 2% of women contaminated through the use of immunoglobulin evolved to cirrhosis over a follow-up period of 17 years [2], while cirrhosis was observed in 51% of patients contaminated through blood transfusion [3].During cirrhosis, patients may develop complications secondary to portal hypertension and/or hepatic insufficiency; they may also have a higher risk for hepatocellular carcinoma (2 to 4% per year) [4,5]. These complications are intimately related to the degree of fibrosis and destructuring of the lobular architecture and, therefore, staging represents the main prognostic marker in patients with chronic hepatitis C.Knowledge about the factors that influence the natural history of hepatitis C is important for the clinical treatment of patients and for the implementation of preventive and therapeutic measures.Our objective was to assess the effect of hostrelated factors on the histological manifestations of

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Section: Discussionmentioning

confidence: 99%

Effect of host-related factors on the intensity of liver fibrosis in patients with chronic hepatitis C virus infection

Costa¹,

Ferraz²,

Perez³

et al. 2002

Braz J Infect Dis

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“…Furthermore, testing other specimens stored under less favorable conditions for a longer time still gave the expected 67% RNA detectability in persons with anti-HCV-positivity. 18 Consequently, we believe that the losses of RNA in TTVS are negligible. A recent study of plasmas stored at Ϫ20°C and Ϫ70°C indicates no significant loss.…”

Section: Discussionmentioning

confidence: 99%

Viral and host factors in early hepatitis C virus infection

et al. 2005

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Since 1980, the Transfusion-transmitted Viruses Study (TTVS) (1974)(1975)(1976)(1977)(1978)(1979)(1980)) has continued to maintain its computerized database and stored sera to enable ongoing study of new transfusion events since the 1970s. Most recently, we have used this resource to study parameters of acute hepatitis C virus (HCV) infection among 94 donor-recipient pairs in which there was transmission. In addition, frequent recipient observations permitted further characterization of the early phase of the infection's course. Donor RNA load ranged from 3.7 to 3,160,000 IU/mL. Onset of recipient viremia was judged from a total of 67 sera collected during the 4th through 8th days posttransfusion; only 2 of the 67 sera were still RNA nonreactive by that time. The recipients' latent periods to an alanine aminotransferase (ALT) elevation of >90 IU/L ranged from 6 to 112 days (median, 46 days) and was shorter with higher donor RNA levels. Descriptors of the recipient's illness showed several strongly positive and negative correlations. The latent period tended to be shorter in the 37% of cases that were clinically overt. Attributes of donors with genotypes 1 and non-1 and subtypes 1a and 1b did not differ significantly. Recipients with genotype 1 strains had shorter latent intervals than non-1 strains. On multivariate analysis, latent period was significantly associated (negatively) only with the highest ALT level during the first 120 days of follow-up (P ‫؍‬ .014). In conclusion, host factors are more important determinants of acute HCV infection dynamics than virus-associated factors. ( I n the past, the most clearly defined cases for study of acute hepatitis C virus (HCV) infection resulted from blood-borne transfusion transmission in populations followed prospectively. This approach identified not only overt cases but also the more numerous subclinical infections. In the last decade, however, screening of blood donors for antibody to HCV (anti-HCV) and then hepatitis C viremia has almost eliminated this route of infection. 1 Fortunately, databases and specimens for several past groups of prospectively followed transfusion recipients are still available. 2 One of these is the Transfusion-transmitted Viruses Study (TTVS), from which it is still possible to obtain new information about HCV infections as increasingly informative laboratory assays have been developed. [3][4][5][6][7] We have identified and further characterized 94 acute transfusion-transmitted HCV cases in which an anti-HCV-negative recipient was infected by a single seropositive donor. We have examined the idea that there could be correlations between donor and recipient parameters, reflecting the replicative capacity or pathogenetic potential of the strain shared between donor and recipient. We have also attempted a thorough description of recipient events during the first 4 months of the infection. Patients and MethodsPopulation. Many details of TTVS have been previously reported. [8][9][10] Briefly, from July 1974 through Octo-

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“…They reported that 17 samples were positive for anti-HCV antibodies, of which 11 were positive for HCV RNA using PCR. Ten of the 11 PCR-positive samples were classified as subtype 1b but no HCV sequences were reported [20]. Here, we provide partial NS5B sequences from two of these 10 isolates, named US1953a and US1953b (genome positions 7939 -8274 relative to the H77 reference strain).…”

Section: Materials and Methods (A) Archived Hepatitis C Virus Isolatesmentioning

confidence: 99%

“…In previous work, Seeff et al [20] screened for antibodies against HCV more than 8000 archived blood samples that had been obtained between 1948 and 1955 from US military recruits. They reported that 17 samples were positive for anti-HCV antibodies, of which 11 were positive for HCV RNA using PCR.…”

Section: Materials and Methods (A) Archived Hepatitis C Virus Isolatesmentioning

confidence: 99%

Evolutionary analysis of hepatitis C virus gene sequences from 1953

Gray

Tanaka

Takebe

et al. 2013

Phil. Trans. R. Soc. B

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Reconstructing the transmission history of infectious diseases in the absence of medical or epidemiological records often relies on the evolutionary analysis of pathogen genetic sequences. The precision of evolutionary estimates of epidemic history can be increased by the inclusion of sequences derived from ‘archived’ samples that are genetically distinct from contemporary strains. Historical sequences are especially valuable for viral pathogens that circulated for many years before being formally identified, including HIV and the hepatitis C virus (HCV). However, surprisingly few HCV isolates sampled before discovery of the virus in 1989 are currently available. Here, we report and analyse two HCV subgenomic sequences obtained from infected individuals in 1953, which represent the oldest genetic evidence of HCV infection. The pairwise genetic diversity between the two sequences indicates a substantial period of HCV transmission prior to the 1950s, and their inclusion in evolutionary analyses provides new estimates of the common ancestor of HCV in the USA. To explore and validate the evolutionary information provided by these sequences, we used a new phylogenetic molecular clock method to estimate the date of sampling of the archived strains, plus the dates of four more contemporary reference genomes. Despite the short fragments available, we conclude that the archived sequences are consistent with a proposed sampling date of 1953, although statistical uncertainty is large. Our cross-validation analyses suggest that the bias and low statistical power observed here likely arise from a combination of high evolutionary rate heterogeneity and an unstructured, star-like phylogeny. We expect that attempts to date other historical viruses under similar circumstances will meet similar problems.

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45-Year Follow-up of Hepatitis C Virus Infection in Healthy Young Adults

Cited by 313 publications

References 29 publications

Effect of host-related factors on the intensity of liver fibrosis in patients with chronic hepatitis C virus infection

Effect of host-related factors on the intensity of liver fibrosis in patients with chronic hepatitis C virus infection

Viral and host factors in early hepatitis C virus infection

Evolutionary analysis of hepatitis C virus gene sequences from 1953

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