Racial differences in liver inflammation and fibrosis related to chronic hepatitis C

Crosse, Kester; Umeadi, Onuora G.; Anania, Frank A.; Laurin, Jacqueline; Papadimitriou, J; Drachenberg, Cinthia; Howell, Charles D.

doi:10.1016/s1542-3565(04)00162-4

Cited by 60 publications

(57 citation statements)

References 24 publications

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“…2,26 In individuals who ultimately fail to control the virus, a wide range of CD4ϩ T cell activity has been reported. 27 In the current study, we found that AAs, who as a group have been previously reported to demonstrate lower rates of spontaneous clearance of acute HCV, milder degrees of liver injury, and lower rates of response to antiviral therapy, [6][7][8][9][10][11][12][13][14][15] show relatively abrogated HCV-specific CD4ϩ T cell responses, yet intact responses to CMV. Considering the importance of CD4ϩ Type 1 helper (Th1) response in promoting the generation of CTLs, it is conceivable that impairment in HCV-specific cell-mediated immunity might result in less hepatic immunopathology but also be associated with a greater likelihood of nonresponse to antiviral therapy.…”

Section: Discussionsupporting

confidence: 54%

“…9 Interestingly, independent cohort studies have demonstrated that, compared to CAs, AAs have milder hepatic necroinflammatory activity and fibrosis progression 10,11 and are 8 times more likely to have normal serum ALT. 12 Indeed, one study estimated that the average time to development of cirrhosis was 22 years in CAs and 40 years in AAs. 12 It is well established that AAs have significantly diminished response rates to IFN-based antiviral therapy.…”

Section: H Epatitis C Virus (Hcv) Infection Affects Approx-mentioning

confidence: 99%

“…12 Indeed, one study estimated that the average time to development of cirrhosis was 22 years in CAs and 40 years in AAs. 12 It is well established that AAs have significantly diminished response rates to IFN-based antiviral therapy. 11,[13][14][15] Differential host immunity to HCV may be implicated as a potential unifying mechanism to explain this set of observations.…”

Section: H Epatitis C Virus (Hcv) Infection Affects Approx-mentioning

confidence: 99%

“…There were no significant differences in age, gender, or risk factors for HCV acquisition between CAs and AAs at enrollment, but AAs had significantly lower serum ALT, in accord with previous reports. 11,12 In order to test the hypothesis that AAs have relatively diminished HCV-specific responses, we used sensitive IFN-␥ ELISPOT assays to quantify CD4ϩ T cell responses to individual recombinant HCV antigens and to CMV. As described in Patients and Methods, we used recombinant proteins derived from genotype 1a (E2, NS4, and NS5) and 1b (core and NS3).…”

Section: Aas Demonstrate Decreased Hcv-specific But Intact Cmv-specifmentioning

confidence: 99%

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Selective decrease in hepatitis C virus-specific immunity among African Americans and outcome of antiviral therapy

Rosen

Weston

et al. 2007

Hepatology

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Hepatitis C virus (HCV) infection is a leading cause of chronic hepatitis, end-stage liver disease, and hepatocellular carcinoma throughout the world. Considerable evidence indicates that the risk of viral persistence, natural history, and response to antiviral therapy varies among racial groups, but limited data exist on potential mechanisms to account for these differences. Type 1 helper (Th1) responses to HCV proteins and cytomegalovirus (CMV) antigens were examined using a sensitive interferon (IFN)-␥ enzyme-linked immunospot (ELISPOT) assay in 187 Caucasian American (CA) and 187 African American (AA) patients with chronic genotype 1 infection. ELISPOT responses were examined relative to human leukocyte antigen (HLA) class II alleles and outcome of therapy with pegylated IFN and ribavirin. Th1 responses specific to hepatitis C core protein and combined HCV antigens were significantly lower in AAs compared to CAs, but CMV responses were comparable in the 2 races. The HCV difference in immunity remained after adjusting for gender, serum alanine aminotransferase, histologic severity, and viral level, and was not accounted for by the differential prevalence of human leukocyte antigen class II alleles. Pretreatment total HCV-specific CD4؉ T cell response was associated with sustained virologic response (SVR) to pegylated IFN and ribavirin; 43% of patients who had more than 168 ELISPOTs/10 6 peripheral blood mononuclear cells (above background) experienced SVR compared to 28% of those who did not (P ‫؍‬ 0.007). ELISPOT response was independently associated with SVR by multivariable analysis. Conclusion: Compared to CAs, AAs have weaker HCVspecific immunity. Pretreatment HCV-specific immunity is associated with response to combination antiviral therapy. (HEPATOLOGY 2007;46:350-358.)

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Section: Discussionsupporting

confidence: 54%

Section: H Epatitis C Virus (Hcv) Infection Affects Approx-mentioning

confidence: 99%

Section: H Epatitis C Virus (Hcv) Infection Affects Approx-mentioning

confidence: 99%

Section: Aas Demonstrate Decreased Hcv-specific But Intact Cmv-specifmentioning

confidence: 99%

See 2 more Smart Citations

Selective decrease in hepatitis C virus-specific immunity among African Americans and outcome of antiviral therapy

Rosen

Weston

et al. 2007

Hepatology

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“…2,3 However, information on the severity and rates of hepatic fibrosis progression among AAs with HCV has been limited because of the small number of AA patients enrolled in previous studies. [4][5][6][7][8] Assessment of the severity of hepatic fibrosis is an integral part of disease management in patients with chronic HCV infection. Patients with minimal or mild fibrosis appear to progress slowly, and antiviral treatment can be safely delayed or withheld, particularly among patients with HCV genotype 1.…”

mentioning

confidence: 99%

Modeling hepatic fibrosis in African American and Caucasian American patients with chronic hepatitis C virus infection

et al. 2006

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The Risk of Long-term Morbidity and Mortality in Patients With Chronic Hepatitis C

et al. 2014

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The impact of viral load suppression, genotype, race, and other factors on the risk of late-stage liver-related events in patients with hepatitis C (HCV) has been assessed previously using data from small observational cohorts or clinical trials. Data from large real-world practice samples are needed to improve risk factor estimates for late-stage liver events and death in HCV.OBJECTIVE To describe the natural history of HCV in real-world clinical practice. DESIGN, SETTING, AND PARTICIPANTS Observational cohort study. Patients with a detectable viral load (>25 IU/mL) and a recorded baseline genotype were selected from the Veterans Affairs (VA) HCV clinical registry (CCR), which compiles electronic medical records data from 1999 to present.EXPOSURES Risk factors included genotype, race, age, sex, and time to achieving an observed undetected viral load. MAIN OUTCOMES AND MEASURESThe primary outcomes were time to death and time to a composite of liver-related clinical events. Secondary outcomes included the components of the composite clinical outcome. Outcomes were measured using a time-to-event format and were analyzed using Cox proportional hazards models.RESULTS A total of 28 769 of 360 857 unique HCV CCR patients met all study criteria. Only 24.3% of patients received treatment, and 16.4% of treated patients (4.0% of all patients) achieved an undetectable viral load. The unadjusted death rates were 6.8 (95% CI, 6.0-7.7) per 1000 person-years for patients who achieved viral load suppression vs 21.8 (95% CI, 21.5-22.2) deaths per 1000 person-years in patients who did not achieve this goal. Cox model results found that achieving viral suppression reduced risk of the composite clinical end point by 27% (hazard ratio [HR], 0.73 [95% CI, 0.66-0.82]) and the risk of death by 45% (HR, 0.55 [95% CI, 0.47-0.64]). Genotype 2 patients were at significantly lower risk, and genotype 3 patients were at higher risk for all study outcomes relative to genotype 1. Black patients were at lower risk for all liver events than white patients. CONCLUSION AND RELEVANCEAchieving an undetectable viral load was associated with decreased hepatic morbidity and mortality. It remains to be determined whether newer treatment regimens can offer higher response rates with fewer adverse effects in real-world settings.

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Racial differences in liver inflammation and fibrosis related to chronic hepatitis C

Cited by 60 publications

References 24 publications

Selective decrease in hepatitis C virus-specific immunity among African Americans and outcome of antiviral therapy

Selective decrease in hepatitis C virus-specific immunity among African Americans and outcome of antiviral therapy

Modeling hepatic fibrosis in African American and Caucasian American patients with chronic hepatitis C virus infection

The Risk of Long-term Morbidity and Mortality in Patients With Chronic Hepatitis C

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