Emerging therapies for hepatitis C virus (HCV) infection: the importance of HCV genotype

2000 ◽  
Vol 30 (6) ◽  
pp. 644-646
Author(s):  
G. W. McCaughan ◽  
S. I. Strasser
Blood ◽  
1998 ◽  
Vol 92 (9) ◽  
pp. 3486-3488 ◽  
Author(s):  
Cristian Antonescu ◽  
Claude Mayerat ◽  
Alain Mantegani ◽  
Philippe C. Frei ◽  
François Spertini ◽  
...  

2021 ◽  
Vol 21 (4) ◽  
Author(s):  
Faisal Abaalkhail ◽  
Waleed Al-hamoudi ◽  
Ibrahim Altraif ◽  
Hazem Mohamed ◽  
Hassan Aleid ◽  
...  

Background: Kidney transplant (KT) recipients have a high rate of hepatitis C virus (HCV) infection, which can impact long-term graft and patient survival rates. Although direct-acting antivirals (DAAs) are effective for treating HCV, there is limited data on their use in post-KT patients with HCV genotype 4 infection. Objectives: To evaluate the effectiveness and occurrence of adverse events with grazoprevir/elbasvir combination treatment without ribavirin in post-KT patients with HCV genotype 4 infection. Methods: In this case series, nine therapy-naïve adult post-KT patients with HCV genotype 4 infection were recruited. They had stable graft function and received a fixed dose of grazoprevir/elbasvir (50 mg/100 mg) combination without ribavirin daily for 12 weeks. Patients co-infected with hepatitis B virus, HIV, or with evidence of decompensated liver disease were excluded from the study. Patients were monitored for viral load, laboratory values, and adverse events associated with drug treatment. The response was defined by the sustained virologic response at 12 weeks (SVR12) after the end of treatment. Results: All nine patients completed the treatment period and achieved SVR12 with no treatment failure or relapse. Of them, six patients had HCV genotype 4 infection alone, and three had HCV of mixed genotypes 1 and 4. Two (22%) patients showed a rapid HCV clearance at four weeks. No adverse events or serious adverse events were reported. The patients’ renal function was stable during and after the treatment with no deterioration of graft function, and no adjustments to the immunosuppressive therapy were required. Conclusions: Grazoprevir/elbasvir combination without ribavirin is an effective and safe treatment option for post-KT patients with genotype 4 HCV infection.


1997 ◽  
Vol 27 (6) ◽  
pp. 959-965 ◽  
Author(s):  
Francesc X. López-Labrador ◽  
Sergi Ampurdanés ◽  
Xavier Forns ◽  
Antoni Castells ◽  
Juan C. Sáiz ◽  
...  

2003 ◽  
Vol 77 (14) ◽  
pp. 7914-7923 ◽  
Author(s):  
Daniel Candotti ◽  
Jillian Temple ◽  
Francis Sarkodie ◽  
Jean-Pierre Allain

ABSTRACT Hepatitis C virus (HCV) infection is thought to mostly become chronic and rarely resolves. HCV infection was serologically screened in 4,984 samples from Ghanaian blood donors, and 1.3% prevalence was found. At least 53% of confirmed anti-HCV carriers had no detectable viral RNA and were considered to have cleared the virus and recovered from the infection. Confirmation was authenticated by the presence of antibodies specific to at least two viral antigens, mostly NS3 and E2. Reactivity to HCV core antigens was lower in Ghanaian than United Kingdom blood donors. The minority of chronically infected donors carried a viral load significantly lower than an unselected comparative group of United Kingdom blood donors (2.5 × 105 versus 2.9 × 106 IU/ml; P = 0.004). HCV genotype 2 was largely predominant (87%). Sequence clustering was similarly broad in the E1/E2 and NS5 regions. The phylogenetic diversity and the incapacity to distinguish subtypes within genotype 2 in our and others' West African strains suggested that West Africa may be the origin of HCV genotype 2. The genetic diversity extended to the identification of strains clearly separated from known subtypes of genotype 2 and genotype 1. One strain appears to be part of a new HCV genotype. HCV infection in Ghana is characterized by a high rate of recovery and the predominance of broadly divergent genotype 2 strains.


2007 ◽  
Vol 81 (22) ◽  
pp. 12375-12381 ◽  
Author(s):  
Tatsuo Kanda ◽  
Robert Steele ◽  
Ranjit Ray ◽  
Ratna B. Ray

ABSTRACT Beta interferon (IFN-β) expression is triggered by double-stranded RNA, a common intermediate in the replication of many viruses including hepatitis C virus (HCV). The recent development of cell culture-grown HCV allowed us to analyze the IFN signaling pathway following virus infection. In this study, we have examined the IFN-β signaling pathway following infection of immortalized human hepatocytes (IHH) with HCV genotype 1a (clone H77) or 2a (clone JFH1). We observed that IHH possesses a functional Toll-like receptor 3 pathway. HCV infection in IHH enhanced IFN-β and IFN-stimulated gene 56 (ISG56) promoter activities; however, poly(I-C)-induced IFN-β and ISG56 expression levels were modestly inhibited upon HCV infection. IHH infected with HCV (genotype 1a or 2a) exhibited various levels of translocation of IRF-3 into the nucleus. The upregulation of endogenous IFN-β and 2′,5′-oligoadenylate synthetase 1 mRNA expression was also observed in HCV-infected IHH. Subsequent studies suggested that HCV infection in IHH enhanced STAT1 and ISG56 protein expression. A functional antiviral response of HCV-infected IHH was observed by the growth-inhibitory role in vesicular stomatitis virus. Together, our results suggested that HCV infection in IHH induces the IFN signaling pathway, which corroborates observations from natural HCV infection in humans.


1998 ◽  
Vol 36 (4) ◽  
pp. 872-877 ◽  
Author(s):  
Marcel Beld ◽  
Maarten Penning ◽  
Martin McMorrow ◽  
Jozef Gorgels ◽  
Anneke van den Hoek ◽  
...  

Hepatitis C virus (HCV) infection often persists in association with chronic hepatitis. Different factors have been proposed to determine the clinical outcome of HCV infection. The aim of this study was to examine three different factors of HCV infection among injecting drug users. Nineteen untreated HCV seroconverters were tested longitudinally for the presence of HCV RNA by reverse transcriptase (RT) PCR, and results were quantified by the branched-DNA (bDNA) assay. HCV genotypes were determined with the first sample taken after HCV seroconversion. To assess the natural course of infection, serum alanine aminotransferase (ALT) levels were measured at three stages in every individual. The concordance between bDNA and RT-PCR was 98.9%. Three distinct patterns were found, according to the HCV RNA load after seroconversion during a mean follow-up period of 5 years (range, 1 to 8 years). HCV genotype 1a was predominant (52.6%). There was a significant increase in serum ALT levels (mean 55.5 U/liter) in the early phase of HCV infection, compared with basal serum ALT levels before HCV seroconversion and at the end of the follow-up period. Three distinct HCV RNA load profiles were found, without apparent relationship to genotype and serum ALT levels in the first 5 years of HCV infection.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4580-4580
Author(s):  
Yelena Patsiornik ◽  
Mushammat Nesa ◽  
Scott Foss ◽  
Michael Bernstein ◽  
Jack Burton

Abstract Background: Autoimmune hematologic abnormalities are frequent among patients with chronic hepatitis C, possibly related to the lymphotropic nature of hepatitis C virus (HCV). It is generally accepted that B-cells infected with HCV clonally expand and produce autoantibodies, which can explain the high prevalence of serological markers of autoimmunity in patients with chronic HCV infection. We recently reported significantly higher incidence of autoantibodies to RBCs and autoimmune hemolytic anemia (AIHA) in patients with HCV as compared to healthy blood donors. Human immunodeficiency virus (HIV) infection is associated with numerous hematologic manifestations. A review of current literature review indicates that a positive direct antiglobulin test (DAT) has been observed in 20% to 40% patients with clinical AIDS. Overt AIHA in patients with AIDS is rare, but can be lethal due to the lack of adequate bone marrow reserve. Many of these patients are also co-infected with HCV, which tends to make immunologic dysregulation more pronounced. Our current analysis of 68 patients, who are positive for both HIV and HCV showed a higher incidence of RBC autoantibodies and clinical AIHA, compared with patients with hepatitis C or HIV/AIDS only. We hypothesized that patients with coinfection with hepatitis C and HIV with anemia would have a higher incidence of AIHA and, thus, would benefit from DAT testing at baseline to detect potentially severe AIHA. Patients and Method: To test this hypothesis, we conducted a retrospective study to confirm that HCV infection in patients with HIV significantly increases the risk of AIHA. A group of 1056 patients with hepatitis C from our hospital’s database from July 2004 to December 2007 was studied. Of this group, 99 patients were co-infected with HCV and HIV. We also looked for an association, if any, of HCV genotype and clinically significant AIHA. Result: Our data showed that AIHA was diagnosed in 9/1056 patients with hepatitis C. Out of this group 6 (0.57%) patients had hepatitis C infection only and 3 (0.3%) patients had co-infection with HCV and HIV. The Z-test was applied to these data from the two groups (HCV+ and HCV+/HIV+) to determine if they were significantly different from one another. The Z-value was determined to be 2.064, with 1-tail confidence level of 98% and 2-tail confidence level of 96.1%, which gives a P value of 0.039 and 0.02, respectively, for the HepC/HIV co-infected group compared with the group of patients infected with HepC only. However, no association between AIHA and particular HCV genotype was noted. Conclusions: Our results indicate that patients with hepatitis C have a relatively high incidence of AIHA, which is even higher in patients concurrently infected with HIV. No particular genotype of HCV was associated with AIHA. In a view of the potential clinical severity of this condition, there needs to be a high degree of clinical suspicion for possible AIHA in patients with co-infection with hepatitis C and HIV.


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