HCV & African-Americans: response to Pegasys (pegylated Interferon) by
African-Americans

Mitchell Shiffman reported results from an analysis of 1208 patients from international randomized phase 1 & 2 studies in Blacks with chronic HCV.  About 30% had cirrhosis and received either regular IFN or Pegylated IFN (Pegasys).  There were 55 Blacks in this database. Remember no one received ribivarin, they only received IFN monotherapy. Response rates are better with combination therapy of IFN+RBV. Here is a preliminary report but I will follow this with more info so stay tuned. I have to rush to oral session. There are a number of presentations here on response to HCV therapy by Blacks, Hispanics & elderly which I'll report on later.

After 72 weeks, 15% of Blacks taking PEG IFN (n=27) had sustained virologic response, versus 0% taking regular IFN (n=28). In Caucasians,  after 72 weeks 34% had SVR taking PEG IFN (n=522) and 13% had SVR taking regular IFN (n=512).

Also important is the histologic response. Blacks receiving PEG IFN had a 33% histologic response rate (n=15) compared to 61% in Caucasians (n=382). Nonetheless, Blacks did have a histologic response overall although it was less than that seen in Caucasians. For those receiving regular IFN 28% of Blacks (n=18) and 47% of Caucasians (n=331) had a histologic response.

COMPARISON OF EPIDEMIOLOGICAL, CLINICAL, VIRAL AND LIVER HISTOLOGY IN AFRICAN-AMERICAN AND CAUCASIAN HEPATITIS C (HCV) PATIENTS. 
     Gabriel Umeadi, Kester Crosse, Jacqueline Laurin, Frank A Anania, John C Papadimitriou, Cinthia I Drachenberg, Charles D Howell, Univ of Maryland, Baltimore, MD

This study suggests HCV progression may not be as bad in Blacks as Whites, but it is a suggestion that needs to be studied. Perhaps, more importantly this study was small (56 Blacks) and was not conducted in coinfected individuals. HCV disease progression can be significantly worse & more severe when HIV is also present.

Chronic hepatitis C (HCV) infection is 2 times more prevalent in African-Americans than White Americans (3.2% vs 1.8%). They also have been reported to have a higher rate of chronic infection and have higher rate of infection with genotype 1. However, African-Americans are less likely to respond to interferon therapies, and a higher incidence of primary hepatocellular carcinoma and higher death rates due HCV. Paradoxically, others have reported that African-Americans as a group have a lower serum ALT levels, lower degrees of periportal piecemeal necrosis, and a slower rate of hepatic fibrosis. So the goal of this study was to compare the epidemiological, clinical, viral, and histological features of African-American and White-Americans who underwent liver biopsies for during evaluation for chronic HCV (anti-HCV+/serum HCV RNA+) at the University of MD between 1995 and 1998.

Methods: The medical records of 56 African-Americans and 67 Non-Hispanic, White adult patients who were referred for HCV evaluation and who underwent a diagnostic liver biospy were reviewed. Patients referred for liver transplantation were excluded. The age, gender, mode of transmission, HCV genotype, HCV RNA, serum ALT, AST, alkaline phosphatase, total bilirubin, serum iron studies, and Histolgocial Activity Index (HAI) total, periportal hepatocyte necrosis, intralobular necrosis, portal inflammation, and fibrosis scores at the initial presentation were tabulated. Results were expressed as mean ± SEM and compared by two-tailed, unpaired t-test (p < 0.05).

Results: African-Americans were older (mean age 47.2 ± 0.8 vs. 43.5 ± 0.875; p = 0.003; Confidence Interval (CI): 1.25 - 6.12 ) and have shorter estimated duration of infection (a longer duration of infection would suggest a person is more likely to progress; as well, younger age at infection and female gender are associated with less severe progression). In addition, African-Americans were more likely to be infected with HCV genotype 1 (91.6% vs. 67.8%). On the contrary, African-americans exhibited significantly lower serum ALT (83.4 ± 6.6 vs. 120.1 ± 10.9; p = 0.0065; CI: -63.1 - -10.5) and serum iron (103.6 ± 7.3 vs. 132.1 ± 9.5; p = 0.02; CI: -52 - -4.9) levels, and a trend toward lower degrees of periportal inflammation and hepatocyte necrosis (HAI I score: 2.2 ± 0.18 vs. 2.75 vs. 0.27; p = 0.10; CI: -1.2 - 0.124). African-Americans and White-Americans had similar modes of HCV transmission and frequency of alcohol abuse, serum AST, alkaline phosphatase, bilirubin, albumin, serum HCV RNA levels, total HAI score and similar degrees of intralobular necrosis, portal inflammation, and fibrosis. Only 3 subjects in each group had cirrhosis (NS).

Conclusion: African- Americans were older at presentation and had a higher prevalence of HCV genotype 1 infection, but exhibit lower indices of liver inflammation hepatocyte damage than White patients. These results are similar to those reported previously by Wiley et al. (Gastro. 118 (4pt. 1): A1012, 2000), though the low incidence of cirrhosis precludes any inferences regarding the fibrosis rate. Theoretically, the lower iron burden and a tendency toward less periportal piecemeal necrosis inflammatory activity could decrease rates of hepatic fibrosis in African-Americans. However, longitudinal studies of well-defined cohorts will be necessary to determine whether the natural history of HCV is different in African-Americans.

At the DDW conference in the Spring of 2000, Thelma Wiley, MD, from the University of Illinois, Chicago reported in an oral presentation on her findings in a retrospective chart review of African Americans at her hospital .  She is the Medical Director of Liver Transplant at the Digestive Diseases and Liver Center at the UIC Medical Center. She found that African Americans progressed more slowly to cirrhosis than caucasians, and less African Americans had cirrhosis than caucasians.  However, its been previously reported that African Americans have a higher rate of liver cancer. She was unable to explain this difference. There were a number of inconsistencies due to inherent biases in the data and its retrospective collection making interpretation difficult. For example, 19% of the patients were excluded due to no records of biopsy, and there were less men in the analysis than women. Female gender is associated with less severe disease progression

Wiley's findings were similar to Howell's reported at AASLD this past month. Because there is little data on the natural history of HCV in African-Americans she compared HCV progression among 355 of 438 whites and African Americans (the ratio was about 2:1 blacks to whites). The others were excluded due to inadequate biopsy information or coinfection with HBV or HIV. The presumed date of initial exposure to HCV was based on the date of transfusion or needlestick, or age of initiation of injection drug use. Histological features were then compared on the basis of race and duration of infection. Liver biopsies were read blindly by pathologist, not knowing patient or clinical history. On average, African-Americans were significantly older than whites (50 vs 46 years) and African-Americans had a significantly longer duration of HCV (26 vs 23 years) at the time of liver biopsy. Whites had a significantly higher percentage of men than blacks (67% vs 53%). These factors are relevant as younger age at infection, female gender, and shorter duration of infection are associated with a less severe disease progression in studies of caucasians.

However, when categorized by decade of infection, mean ALT levels were lower and cirrhosis was less common in African American than white patients. Overall she reported cirrhosis was seen less often in blacks than whites (23% vs 30%, but this was not statistically significant. Since coinfection with HIV can accelerate HCV progression, this must also be considered. After 2 decades of infection, cirrhosis was present in 0% of African Americans vs. 26% whites. These differences insignificantly persisted in both the third (18% and 31%) and fourth decade (22% and 50%) of infection. African-Americans appeared to have lower fibrosis scores. Due to the retrospective nature of the analysis, these data may be biased. Most prospective studies on the natural history of HCV have included too few African Americans for meaningful comparisons of outcomes.

In Wiley's portion of the NIH meeting summary she wrote for Gastroenterolgy, (see NATAP summary of this report) she says:

Similar results were presented by Bonacini et al. (University of Southern California, Los Angeles, personal communication, December 1999). Among 291 patients who underwent liver biopsy, the estimated rate of fibrosis progression was lower in the 53 African Americans (0.055 stages per year) than 116 whites (0.096 stages per year). Progression of fibrosis was also more rapid among human immunodeficiency virus (HIV)-coinfected patients, but this did not account for the racial and ethnic differences.

There are many shortcomings of retrospective analyses of disease progression based on presumed time of exposure, particularly when the date of exposure is several decades before clinical presentation. Nevertheless, these 2 analyses suggest that liver fibrosis evolves more slowly in African American than in white patients with HCV.