Peginterferon and Ribavirin Treatment in African American and Caucasian American Patients With Hepatitis C Genotype 1

Conjeevaram, Hari S.; Fried, Michael; Jeffers, Lennox J.; Terrault, Norah A.; E., Wiley-Lucas, Thelma; Afdhal, Nezam H.; Brown, Robert S.; Belle, Steven H.; Hoofnagle, Jay H.; Kleiner, David E.; Howell, Charles D.

doi:10.1053/j.gastro.2006.06.008

Cited by 434 publications

(454 citation statements)

References 16 publications

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“…5 Participants had to meet specific selection criteria: all had mild fibrosis, were interferon-treatment naïve and were infected with genotype-1 HCV. Future studies examining a broader patient population are warranted.…”

Section: Discussionmentioning

confidence: 99%

“…Details of this study have been published previously. 5 All subjects were born in the United States and race was determined by a self-administered questionnaire.…”

Section: Study Populationmentioning

confidence: 99%

“…3,4 However, successful clearance of the virus with therapy can depend upon many factors including viral factors such as viral genotype and viral load at the start of treatment, and host factors including patient age, gender and the presence of co-morbidities such extensive fibrosis or cirrhosis and hepatic steatosis. 3,5 The race to which the patient belongs appears to strongly influence the response to therapy. We and others have reported African Americans (AAs) having significantly lower response rates to combination pegylated interferon (peginterferon) and ribavirin therapy compared to Caucasian Americans (CAs).…”

Section: Introductionmentioning

confidence: 99%

“…We and others have reported African Americans (AAs) having significantly lower response rates to combination pegylated interferon (peginterferon) and ribavirin therapy compared to Caucasian Americans (CAs). [5][6][7] This racial difference and the broad spectrum of response to therapy suggest a possible role for host genetic diversity in the response to anti-HCV therapy.…”

Section: Introductionmentioning

confidence: 99%

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Associations between the human MHC and sustained virologic response in the treatment of chronic hepatitis C virus infection

Rhodes

Erlich

et al. 2008

Genes Immun

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The human major histocompatability complex (MHC) genes encode the human leukocyte antigens, which are important in antigen presentation and regulation of CD8 þ and CD4 þ T cells. Response to therapies in hepatitis C virus (HCV) infection is highly variable (30-80%) and lower response rates have been reported among African Americans (AA; B30%) compared to Caucasian Americans (CA; B50%) infected with genotype-1 viruses. We evaluated whether MHC gene variants were associated with response to therapy and racial differences in AA and CA sustained virologic response (SVR) rates. We genotyped alleles at 8 MHC loci: 3 class I (A, B and C) and 5 class II (DRB1, DQA1, DQB1, DPA1 and DPB1) loci in 373 individuals (179 AA and 194 CA) with genotype-1 HCV infections, who were treated with peginterferon-a-2a and ribavirin. We observed carriage of A*02 (RR ¼ 1.33(1.08-1.64); P ¼ 0.008), B *58 (RR ¼ 1.84(1.24-2.73); P ¼ 0.002) and DPB1*1701 (RR ¼ 1.57(1.09-2.26); P ¼ 0.015) to be associated with SVR after adjustment for other predictors of response. In analysis of AA and CA subgroups separately, we observed potential, though not statistically significant, differences in these MHC associations. Variation in the immunogenetic background of HCV-infected individuals might account for some observed variation in viral-specific immunity and courses of disease. In this regard, future studies examining broader patient populations are warranted.

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Section: Discussionmentioning

confidence: 99%

“…Details of this study have been published previously. 5 All subjects were born in the United States and race was determined by a self-administered questionnaire.…”

Section: Study Populationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Associations between the human MHC and sustained virologic response in the treatment of chronic hepatitis C virus infection

Rhodes

Erlich

et al. 2008

Genes Immun

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“…During a discussion about the probabilities of sustained virological response versus the potential side effects associated with combination antiviral therapy, I would assess the patient's level of enthusiasm for undergoing treatment. For African American patients, the likelihood of sustained virological response is significantly lower than Caucasian patients and this must be factored into the discussion as well 10 .…”

Section: Recommendationsmentioning

confidence: 99%

Hepatitis C Infection With Normal Liver Chemistry Tests

Fried¹

2008

Clinical Gastroenterology and Hepatology

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A 50 y/o man was recently diagnosed with chronic hepatitis C after a life insurance physical. He was very surprised by the diagnosis since he led an active lifestyle, exercised regularly, and did not smoke nor drink any alcohol, except a glass of wine once or twice per month. He had experimented with injecting drugs during his freshman year at college. Over the last 5 years, he had undergone regular physicals and never was told of any "liver problems". In reviewing laboratory data from his referring provider, liver enzymes had been checked on two previous annual physicals with serum ALT activities of 44 and 41 U/L. Physical examination shows a healthy male, BMI =24, without any stigmata of chronic liver disease. Currently, serum ALT activity is 44 U/L and HCV RNA is >700,000 IU/mL with genotype 1. Platelet count was 244,000 cells/mm 3 . The DilemmaThis patient is a generally healthy man who was likely infected with chronic hepatitis C for over 30 years prior to the consultation. Despite the prolonged duration of infection, he had no signs or symptoms of hepatitis C or advanced liver disease. There is historical evidence that his serum ALT activities have been persistently within the normal range. When confronted with such an individual, clinicians may speculate that aggressive treatment of hepatitis C in this vigorous patient is unwarranted. However, further evaluation and management can be planned only after considering the natural history of chronic hepatitis C infection with persistently normal ALT levels and the outcome of therapy in these patients. Defining normal serum ALT activityElevations of serum alanine amontransferase (ALT) and aspartate aminotransferases (AST) activity serve as important markers for liver injury. The finding of an abnormal ALT in a patient, even in the absence of clinical signs or symptoms, should prompt further evaluation for occult liver disease. Hereditary hemochromatosis, chronic viral hepatitis, and nonalcoholic steatohepatitis are frequently overlooked causes of asymptomatic ALT abnormalities that could have serious consequences over time. In order to define "abnormal ALT" which would prompt clinical investigation, healthcare providers must be confident in the definition of "normal" ALT, a value below which they can be secure that liver disease is unlikely. However, despite the importance of these definitions to general medical care and the seemingly simple dichotomy that should be represented by a laboratory test above or

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Effect of Silymarin (Milk Thistle) on Liver Disease in Patients With Chronic Hepatitis C Unsuccessfully Treated With Interferon Therapy

Fried

Navarro

Afdhal

et al. 2012

JAMA

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146

136

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Peginterferon and Ribavirin Treatment in African American and Caucasian American Patients With Hepatitis C Genotype 1

Abstract: AA with chronic hepatitis C genotype 1 have lower rates of virologic response to peginterferon and ribavirin than CA. These differences are not explained by disease characteristics, baseline viral levels, or amount of medication taken.

Cited by 434 publications

References 16 publications

Associations between the human MHC and sustained virologic response in the treatment of chronic hepatitis C virus infection

Associations between the human MHC and sustained virologic response in the treatment of chronic hepatitis C virus infection

Hepatitis C Infection With Normal Liver Chemistry Tests

Effect of Silymarin (Milk Thistle) on Liver Disease in Patients With Chronic Hepatitis C Unsuccessfully Treated With Interferon Therapy

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