The impact of interferon plus ribavirin on response to therapy in black patients with chronic hepatitis C

doi:10.1053/gast.2000.19289

Gastroenterology

Volume 119, Issue 5, November 2000, Pages 1317-1323

https://doi.org/10.1053/gast.2000.19289 Get rights and content

Abstract

Background & Aims: Black patients with chronic hepatitis C have lower response rates than white patients to interferon monotherapy. The factors responsible for these differences are unknown, as is the impact of combination antiviral therapy on responsiveness among ethnic groups. We evaluated the impact of race on response to therapy in these patients. Methods: A total of 1744 patients with chronic hepatitis C were randomized in 2 recent clinical trials to receive 24 or 48 weeks of interferon monotherapy or interferon-ribavirin combination therapy. Results: Sustained virologic responses occurred in 27% of 1600 whites, 11% of 53 blacks (P = 0.01 vs. white), 44% of 32 Asians, and 16% of 27 Hispanics. No black patient had a sustained virologic response to interferon monotherapy, but 20% and 23% had sustained responses to 24 and 48 weeks, respectively, of combination therapy. Among black patients, 96% had hepatitis C genotype 1 compared with 65% of white subjects (P < 0.0001). Sustained response rates were similar for black and white patients with genotype 1 infection (23% vs. 22%, respectively). Compared with whites, black patients were older, weighed more, and had higher median Histologic Activity Index scores but did not differ in sex, baseline alanine aminotransferase or hepatitis C virus (HCV)-RNA levels, degree of fibrosis or percentage with cirrhosis, or other demographic variables. White subjects had a significantly greater reduction in HCV-RNA levels than blacks at weeks 4, 12, 24, and 48 of therapy, but only for black patients treated with interferon monotherapy. The decreased reduction of HCV-RNA reduction among blacks was eliminated by combination therapy. Conclusions: These observations suggest that the impaired responsiveness of black patients to interferon monotherapy can be overcome partially by combination interferon-ribavirin therapy.

GASTROENTEROLOGY 2000;119:1317-1323

Section snippets

Patient selection

We evaluated individual patient data from 1744 patients enrolled in 2 randomized trials described in detail previously.9, 10 All patients were randomized to 1 of 4 treatment groups, allowing for balance and stratification based on the presence or absence of cirrhosis, pretreatment serum HCV-RNA level, and HCV genotype. The 4 groups received interferon alfa-2b (Intron A; Schering Plough, Kenilworth, NJ) plus placebo, either for 24 (n = 231) or 48 weeks (n = 503), or the combination of interferon

Results

Of the 1744 patients who were randomized and treated, 1600 were white, 53 were black, 27 were Asian, 32 were Hispanic, and 32 were of other racial origins. The demographic characteristics of the 4 racial groups are summarized in Table 1.

. Baseline characteristics in different racial groups

Empty Cell	White (n = 1600)	Black (n = 53)	Asian (n = 27)	Hispanic (n = 32)
Mean age [yr (range)]	43 (19–75)^a	46 (32–59)^b	45 (21–79)	45 (32–68)
Sex (M/F)	1042/558	36/17	22/5	24/8
Estimated length of infection (yr)^e	17	18	21	21
Weight (kg)	79

Discussion

Understanding factors that aid in predicting response to therapy in HCV infection is important. Baseline viral factors have consistently been identified as predictors of response to interferon-based therapies.9, 10, 18, 19 A recent report shows that black patients have low response rates when treated with interferon.¹¹ In our analysis of the largest group of black patients to date, we confirmed the poor response rate to interferon monotherapy in black patients. No black patients achieved a

Acknowledgements

The authors thank Dr. Z. D. Goodman (Armed Forces Institute of Pathology, Washington, D.C.) for acting as the pathologist for this study; B. Sangheve for statistical analyses; and Elvia Nunez (Scripps Clinic) for editing and preparing the manuscript.

References (26)

T Poynard et al.
Randomised trial of interferon alpha 2b plus ribavirin for 48 weeks or for 24 weeks versus interferon alpha 2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus
Lancet
(1998)
MJ Tong et al.
Prediction of response during interferon alfa 2b therapy in chronic hepatitis C patients using viral and biochemical characteristics: a comparison
Hepatology
(1997)
M Martinot-Peignoux et al.
Pretreatment serum hepatitis C virus RNA levels and hepatitis C virus genotype are the main and independent prognostic factors of sustained response to interferon alfa therapy in chronic hepatitis C
Hepatology
(1995)
DT Lau et al.
Long-term follow-up of patients with chronic hepatitis B treated with interferon alfa
Gastroenterology
(1997)
M Alter et al.
The prevalence of hepatitis C virus in the United States, 1988 through 1994
N Engl J Med
(1999)
Anonymous
National Institutes of Health Consensus Development Conference Panel Statement: management of hepatitis C
Hepatology
(1997)
K Detre et al.
Liver transplantation for chronic viral hepatitis
Viral Hepat Rev
(1996)
JB Wong et al.
Pretreatment evaluation of chronic hepatitis C: risks, benefits, and costs
JAMA
(1998)
RS Koff
Therapy of hepatitis C: cost-effectiveness analysis
Hepatology
(1997)
RS Koff
Impaired health-related quality of life in chronic hepatitis C: the how, but not the why
Hepatology
(1999)

HL Bonkovsky et al.

Reduction of health-related quality of life in chronic hepatitis C and improvement with interferon therapy

Hepatology

(1999)

ZM Younossi et al.

Cost effectiveness of interferon alpha 2b combined with ribavirin for the treatment of chronic hepatitis C

Hepatology

(1999)

JG McHutchison et al.

Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C

N Engl J Med

(1998)

Cited by (167)

A Systematic Review of Race and Ethnicity in Hepatitis C Clinical Trial Enrollment
2016, Journal of the National Medical Association
The African American/Black population in the United States (US) is disproportionately affected by hepatitis C virus (HCV) and has lower response rates to current treatments. This analysis evaluates the participation of African American/Blacks in North American and European HCV clinical trials. The data source for this analysis was the PubMed database.
Randomized controlled clinical trials (RCT) on HCV treatment with interferon 2a or 2b between January 2000 and December 2011 were reviewed. Inclusion criteria included English language and participants 18 years or older with chronic HCV. Exclusion criteria included non-randomized trials, case reports, cohort studies, ethnic specific studies, or studies not using interferon-alfa or PEG-interferon. Of the 588 trials identified, 314 (53.4%) fit inclusion criteria. The main outcome was the rate of African American/ Black participation in North American HCV clinical trials. A meta-analysis comparing the expected and observed rates was performed.
Of the RCT's that met search criteria, 123 (39.2%) reported race. Clinical trials in North America were more likely to report racial data than European trials. Racial reporting increased over time. There was a statistically significant difference among the expected and observed participation of African Americans in HCV clinical trials in North America based on the prevalence of this disease within the population.
The burden of HCV among African Americans in North America is not reflected in those clinical trials designed to treat HCV. Research on minority participation in clinical trials and how to increase minority participation in clinical trials is needed.
Viral Hepatitis
2014, Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases
Hepatitis B and C in African Americans: Current status and continued challenges
2014, Clinical Gastroenterology and Hepatology
Viral hepatitis remains a public health concern in the United States, resulting in excess morbidity and mortality for the individual and representing a burden to societies as evidenced by billions of dollars in health care expenditures. As with many chronic diseases, race and ethnicity influence various aspects of disease pathogenesis, including mechanisms of persistence, disease progression, disease sequelae, and response to therapy. For hepatitis B and C infections, African Americans disproportionately bear a large burden of disease in the United States. The role and importance of African American race, however, have been less well-characterized in the literature among the population of viral hepatitis–infected individuals. The differences in epidemiology, manifestations of liver disease, response to therapy, and differential trends in liver transplantation in African Americans compared with other racial and ethnic groups deserve special attention. This review will address the current status of hepatitis B and C infection in African Americans in the United States and identify some of the remaining challenges in diagnosis, characterization of natural history, and treatment. For the purposes of this review, the terms African American and black will be used interchangeably throughout the text.
Direct acting antivirals for the treatment of hepatitis C in ethnic minority populations
2018, Expert Opinion on Pharmacotherapy
Treatment optimization for HIV/HCV co-infected patients
2017, Therapeutic Advances in Infectious Disease
Safety and efficacy of ledipasvir-sofosbuvir in black patients with hepatitis C virus infection: A retrospective analysis of phase 3 data
2016, Hepatology

View all citing articles on Scopus

^☆: Address requests for reprints to: John G. McHutchison, M.D., Division of Gastroenterology/Hepatology (203N), Scripps Clinic and Research Foundation, 10666 North Torrey Pines Road, La Jolla, California 92037. e-mail: [email protected]; fax: (858) 554-9947.

^☆☆: Supported in part by research grants from Schering Plough Corp. (Kenilworth, New Jersey) and the General Clinical Research Center grants at Scripps Clinic (MO1-RR00833) and the Massachusetts General Hospital (MO-1RR01066).

View full text

Liver, Pancreas, and Biliary TractThe impact of interferon plus ribavirin on response to therapy in black patients with chronic hepatitis C☆,☆☆

Abstract

Section snippets

Patient selection

Results

Discussion

Acknowledgements

Lancet

Hepatology

Hepatology

Gastroenterology

The prevalence of hepatitis C virus in the United States, 1988 through 1994

N Engl J Med

National Institutes of Health Consensus Development Conference Panel Statement: management of hepatitis C

Hepatology

Liver transplantation for chronic viral hepatitis

Viral Hepat Rev

Pretreatment evaluation of chronic hepatitis C: risks, benefits, and costs

JAMA

Therapy of hepatitis C: cost-effectiveness analysis

Hepatology

Impaired health-related quality of life in chronic hepatitis C: the how, but not the why

Hepatology

Reduction of health-related quality of life in chronic hepatitis C and improvement with interferon therapy

Hepatology

Cost effectiveness of interferon alpha 2b combined with ribavirin for the treatment of chronic hepatitis C

Hepatology

Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C

N Engl J Med

Liver, Pancreas, and Biliary Tract
The impact of interferon plus ribavirin on response to therapy in black patients with chronic hepatitis C☆,☆☆